
NOV 20 1897 




LIBRARY OF CONGRESS. 



Chap ...___r:. Copyright No... 



Shelf.^_S_. 



UNITED STATES OF AMERICA. 



I, 



A MANUAL 



OF 



CLINICAL DIAGNOSIS 

BY MEANS OF MICROSCOPIC AND 
CHEMICAL METHODS, 



FOR 



STUDENTS, HOSPITAL PHYSICIANS, AND PRACTITIONERS. 



7 



CHAELES E. 'SIMON, M.D., 

LATE ASSISTANT RESIDENT PHYSICIAN, JOHNS HOPKINS HOSPITAL, BALTIMORE \ 
FELLOW OF THE AMERICAN ACADEMY OF MEDICINE. 



SECOND EDITION, REVISED AND ENLARGED. 



With 133 Illustrations on Wood and 14 Colored Plates. 




LEA BROTHERS & CO., 

PHILADELPHIA AND NEW YORK 
1897. 



OCT 27 1897 )) 

(odW^ c:^ * ,^J 



rj^ 



b 



-<o 



,<^ v 



Entered according to the Act of Congress in the year 1897, by 

LEA BROTHERS & CO., 
In the Office of the Librarian of Congress. All rights reserved. 



DOR NAN, PRINTER. 



TO 



HIS WIFE, 



WHO HAS SO FAITHFULLY AIDED IN ITS PREPARATION. 



THIS VOLUME IS AFFECTIONATELY DEDICATED 



BY THE 



AUTHOR. 



PREFACE TO THE SECOND EDITION. 



In the present edition the endeavor has been made to bring the 
volume thoroughly up to date. The parasitology and bacteriology of 
the blood, saliva, feces, urine, and vaginal discharge have been almost 
entirely rewritten. New methods of chemical examination which 
have appeared since the publication of the first edition have been 
embodied in the work, and some of the older and complicated ones 
omitted. Throughout the text numerous additions have been made, 
so that the size of the volume has been increased by about fifty 
pages. The examination of the cerebro-spinal fluid and its clinical 
significance have been carefully considered. Some of the illustra- 
tions have been replaced by more accurate ones, and others entirely 
new have been added where they appeared to be of value to the 
student. 

In conclusion, the writer wishes to thank the medical profession 
for the kind manner in which the first edition has been received. 

CHARLES E. SIMON. 

1302 Madison Avenue, Baltimore, Md., 1897* 



PREFACE TO THE FIRST EDITION 



It is curious to uote that, notwithstanding the great importance 
of clinical chemistry and microscopy, but little attention is paid to 
these subjects, either by hospital physicians or by those engaged in 
general practice. This lack of interest is referable primarily to the 
fact that a systematic study of these branches has hitherto been 
greatly neglected, not only in American medical schools, but also 
in those of Europe. 

It is no rarity to hear physicians in general practice claim that 
they are too busy to conduct careful examinations of the urine, 
sputum, blood, gastric juice, etc. Would it not be reasonable to 
suppose, however, that a physician who is overwhelmed with work 
to such an extent that he cannot find the time to make use of aids 
in diagnosis which are quite as important as the stethoscope, the 
laryngoscope, or the ophthalmoscope, would be in a position to 
employ an assistant in his laboratory ? The younger practitioner 
is certainly not placed in such a dilemma, and it is a fair assump- 
tion that he could successfully compete with his more experienced 
colleague, in matters of diagnosis at least, were he to familiarize 
himself sufficiently with laboratory methods of diagnosis. 

The time is at hand when the practice of medicine is becoming 
what it was long ago, but then unjustly, called, a true science and 
art. No continuing success can be built on empiricism or upon 
the proportion of guesswork which is inseparable from dependence 
upon " the experienced eye." " Diagnosis " is now the password 
in medical science. A knowledge of electro-diagnosis, of ophthal- 
moscopy, of laryngoscopy, etc., is at the present day a sine qua non 
for accurate diagnosis. Equally important at all times, and fre- 
quently even more important, is a knowledge of clinical chemistry 
and microscopy. It is inconceivable that a physician can rationally 
diagnose and treat diseases of the stomach, intestines, kidneys, and 
liver, etc., without laboratory facilities. 

It has been the author's aim to present to students and physicians 



yiii PREFACE TO FIRST EDITION. 

those facts in clinical chemistry and microscopy which are of prac- 
tical importance. With the hope of exciting interest in these unjustly 
neglected subjects, he has not confined himself to bare statements of 
facts, which must in themselves be dry and uninteresting, but he 
has attempted to point out the reasons which have led up to the 
conclusions reached. 

Chemical and microscopic methods are described in detail, so that 
the student and practitioner who has not had special training in 
such manipulations will be enabled to obtain satisfactory results. 

The subject-matter covers the examination of the blood, the secre- 
tions of the mouth, the gastric juice, feces, nasal secretion, sputum, 
urine, transudates, exudates, cystic contents, semen, vaginal dis- 
charges, and milk. In every case a description of normal material 
precedes the pathologic considerations, which latter in turn are 
followed by an account of the methods used in examination. A 
glance at the table of contents will furnish an idea of the various 
subjects considered under each heading. 

It was not deemed advisable to burden the volume with a com- 
plete enumeration of the various literary sources consulted by the 
author in its preparation, and the names of the various investigators 
meutioned in the text have been largely introduced as a matter of 
historical interest. 

In conclusion it is the agreeable duty of the author to express his 
sincerest thanks to his wife for assistance without which this volume 
could not have been written, and likewise for those illustrations 
which are original ; to Dr. William H. Welch for his kindness 
in placing the former Hygienic Laboratory of the Johns Hopkins 
Hospital at his disposal during the years 1892 and 1893 ; to Dr. 
W. Milton Lewis for much valuable aid in the correction of the 
manuscript and proof-sheets; and to Messrs. Lea Brothers & Co. 
for the typographical excellence of the work, the extremely satisfac- 
tory reproduction of the drawings, and for many acts of courtesy. 

CHARLES E. SIMON. 

Baltimore, Md„ 1896. 



CONTENTS 



CHAPTER I. 












THE BLOOD. 






PAGE 


General considerations 


. 17 


General characteristics of the blood 




17 


color 




17 


odor 




18 


specific gravity . ..... 




18 


determination according to Roy 




19 


determination according to Hammerschlag 




19 


determination according to Schmaltz and Peiper 




20 


indirect estimation of the haemoglobin . 




20 


estimation of the solids of the blood 




20 


reaction ......... 




. 21 


estimation of the alkalinity according to Landois--\ 


r. Jaksch 


22 


estimation of the alkalinity according to Lowy 




. 24 


Chemical examination of the blood .... 




25 


general chemistry of the blood 








25 


blood-pigments 








29 


haemoglobin ..... 








29 


oxy haemoglobin .... 








. 29 


estimation of haemoglobin with FleischPs haemometer 


32 


estimation of haemoglobin with Gowers' haemoglobinometej 


r 35 


haemoglobinaemia 


. 36 


carbon monoxide haemoglobin . 










37 


nitric oxide haemoglobin . 










38 


sulphuretted hydrogen haemoglobin 










38 


carbon dioxide haemoglobin 










38 


haematin ...... 










38 


haemin ...... 










39 


methaemoglobin 










40 


haematoidin ..... 










41 


haematoporphyrin .... 










41 


the spectroscope 










42 


the proteids of the blood .... 










44 


the carbohydrates 










45 


sugar 










4-") 


estimation of the sugar in the blood 










46 


glycogen 










47 


cellulose 










47 


urea 










48 


uraemia ....... 










48 


uric acid and xanthin bases . 










48 


fat and fatty acids ..... 










50 


lactic acid 










51 


biliary constituents 










52 


acetone 










53 



CONTENTS. 



Microscopic examination of the blood ...... 

the red corpuscles 

variations in the size of the red corpuscles 
variations in the form of the red corpuscles 
variations in the number of the red corpuscles 
nucleated red corpuscles ....... 

the leucocytes 

variations in the number of the leucocytes 

physiologic hy perl eucocy tosis ..... 

pathologic hyperleucocytosis ..... 

general differentiation of the various forms of leucocytes 

the anil in -stains 

differentiation of the leucocytes according to their behavior to 
ward anilin-stains 

the drying and staining of blood .... 

staining with eosin ........ 

staining with Ehrlich's tri-glycerine mixture . 

staining with Ehrlich's hsematoxylin-eosin 

staining with Ehrlich's tri-acid stain .... 

staining with Aronsohn and Philips' modified tri-acid stain 

staining with Chenzinsky-Plehn's mixture 

staining with Ehrlich's neutral mixture . . ... 

special staining of basophilic leucocytes 

Neusser's stain for perinuclear basophilic granules . 

the plaques 

the enumeration of the corpuscles of the blood by the method of 
Thoma-Zeiss .... 

enumeration of the red corpuscles . 

enumeration of the white corpuscles 

indirect enumeration of the leucocytes 

the hsematokrit .... 
Bacteriology and parasitology of the blood 

typhoid fever . 

Widal's serum test 



pneumonia 

sepsis 

anthrax . 

acute miliary tuberculosis 

glanders . 

influenza 

relapsing fever 

malaria . 

filariasis . 

distomiasis 



PAGE 

53 

53 
53 

54 
54 
56 
57 
58 
58 
60 
62 
62 

63 
66 
68 
68 
68 
68 
69 
69 
70 
70 
70 
71 

71 

72 
74 
75 
76 
79 
79 
79 
81 
83 
85 
85 
85 
86 
87 
88 
97 
99 



CHAPTER II. 



THE SECRETIONS OF THE MOUTH 

Saliva 

general characteristics .... 
chemistry of the saliva .... 
microscopic examination of the saliva 
pathologic alterations .... 
the saliva in special diseases of the mouth 

catarrhal stomatitis .... 

ulcerative stomatitis 

gonorrheal stomatitis 

thrush 



101 
101 
101 
103 
105 
106 
106 
106 
106 
106 



CONTENTS. 



m 



Tartar .... 

Coating of the tongue . 

Tuberculosis of the mouth 

Actinomycosis 

Coating of the tonsils . 

pharyngomycosis leptoth 

diphtheria 



page 

Hi? 
107 
108 
108 
108 
108 
109 



CHAPTER III. 



THE GASTRIC JUICE AND THE GASTRIC CONTENTS. 

The secretion of the gastric juice . . . . . . . .112 

Test-meals 113 

the test-breakfast of Ewald and Boas 114 

the test-dinner of Eiegel 114 

the double test-meal of Salzer . . . . . . .114 

the test-breakfast of Boas 114 

The stomach-tube 115 

contraindications to the use of the tube 115 

the introduction of the tube . . . . . . . .115 

General characteristics of the gastric juice 118 

Amount 119 

Chemical examination of the gastric juice ...... 120 

chemical composition of the gastric juice ..... 120 

the acidity of the gastric juice 120 

determination of the acidity of the gastric juice .... 122 

the source of the hydrochloric acid . . . . . 125 

significance of the free hydrochloric acid 126 

the amount of free hydrochloric acid 128 

euchlorhydria .128 

hypochlorhydria . . . ... . . . 129 

anachlorhydria 129 

hyperchlorhydria 129 

test for free acids 129 

tests for free hydrochloric acid 130 

the dimethyl-amido-azo-benzol test ...... 130 

the phloroglucin-vanillin test . . . . . . . 131 

the resorcin test ......... 132 

the methyl- violet and emerald-green test . . . .132 

the tropaeolin test 132 

Mohr's test 133 

the benzopurpurin test 133 

the combined hydrochloric acid 134 

the quantitative estimation of hydrochloric acid .... 135 

Topfer's method . 135 

Martius and Liittke's method 137 

Leo's method 140 

the ferments of the gastric juice and their zymogens . . . 141 

pepsin and pepsinogen ........ 141 

tests for pepsin and pepsinogen. ..... 143 

quantitative estimation ....... 144 

chymosin and chymosinogen ....... 145 

tests for chymosin and chymosinogen .... 146 

quantitative estimation 146 

the products of gastric digestion 147 

the digestion of native albumins . . . . . .147 

the digestion of albuminoids ....... 149 



Xll 



CONTESTS. 



Chemical examination of the gastric juice — Continued. 

the digestion of carbohydrates 

the digestion of fats .... 
analysis of the products of albuminous digestion 
analysis of the products of carbohydrate digestion 
lactic acid 

mode of formation and clinical significance 

tests for lactic acid 

UrTelmann's test .... 
Kelling*s test ..... 

Strauss* test 

Boas* test 

quantitative estimation of lactic acid according to Boas' method 
the fatty acids 

mode of formation and clinical significance 

tests for butyric acid .... 

tests for acetic acid 

quantitative estimation of the fatty acids 

quantitative estimation of the organic acids 

gases 

acetone 

ptomains and toxalbumins 
vomited material 

food-material . 

mucus .... 

gastrosuccorrho3a mucosa . 

saliva .... 

bile 

pancreatic juice 

blood .... 

test of Miiller and Weber 

pus 

stercoraceous material 

parasites .... 

odor .... 

Microscopic examination of the gastric 
the Boas-Oppler bacillus ~ . 

sarcina; 

shreds of mucous membrane . 
tumor particles 
Examination of the motor power of the stomach 

Leube's method 

the salol test of Ewald and Sievers 
Examination of the resorptive power of the stomach 
Indirect examination of the gastric juice 

Giinzburg's method 

the author's method 



contents 



PAGE 
149 

151 

152 
153 
153 

156 
157 
157 
158 
159 
161 
161 

163 
163 
163 

166 
167 

167 
167 

16V< 
169 
170 

170 
170 

17" 
171 
171 
171 
172 
172 
173 
173 
174 
175 
175 

176 
176 
177 
177 
178 



CHAPTER IV 

THE FECES. 



Definition .... 
Examination of the normal feces 
general characteristics 

number of stools 

amount 

consistence and form 



181 
181 
181 
181 

: ; : 
182 



CONTENTS. 



Mil 



Examination of the normal feces — Continued. 
odor 
color 
macroscopic constituents 
alimentary detritus 
foreign bodies . 
microscopic constituents 

constituents derived from food 

morphologic elements derived from the alimentary 

crystals 

parasites . 

vegetable parasites 
fungi . 
schizomycetes 
bacteria 
chemistry of normal feces 
reaction . 
general composition 
phenol, indol, and skatol 
fatty acids 
cholesterin 
the biliary acids 
pigments . 
Pathology of the feces . 
general characteristics 
number of stools 
consistence and form 
amount 
odor 

reaction . 
color 
macroscopic constituents 
alimentary constituents 
mucus and mucous cylinders 
biliary and intestinal concretions 
coproliths 

analysis of gall-stones 
microscopic examination 
technique 
remnants of food 
mucus 
epithelium 
red blood -corpuscles 
leucocytes 
crystals 
animal parasites 
protozoa . 

amoeba coli 
cercomonas 
trichomonas 
megastoma entericmn 
balantidium coli 
vermes 

taenia saginata . 
taenia solium 
taenia nana 
taenia diminuta . 
taenia cucumerina 



canal 



PAGE 

L82 

182 
183 
183 
183 
183 
183 
185 
185 
187 
187 
187 
187 
187 
189 
189 
189 
191 
193 
195 
196 
197 
197 
197 
197 
198 
199 
199 
199 
199 
201 
201 
203 
204 
205 
205 
205 
205 
206 
207 
207 
207 
208 
208 
209 
209 
210 
214 
214 
216 
216 
217 
217 
218 
220 
220 
220 



XIV 



CONTENTS. 



Pathology of the feces — Continued. 
bothriocephalus latus 
krabbea grandis 
distoma hepaticum . 
distoma lanceolatum 
distoma Buskii . 
distoma sibiricum 
distoma spatulatum . 
ascaris lumbricoides . 
ascaris mystax . 
oxyuris vermicularis 
anchylostoma duodenale 
trichocephalus hominis 
trichina spiralis 
anguillula intestinalis 
insecta .... 

chemistry of the feces 
The physiology of diarrhoea and constipation 

diarrhoea 

constipation . 
The feces in various diseases of the intestinal 

acute intestinal catarrh . 

chronic intestinal catarrh 

cholera nostras 

summer diarrhoea of 

dysentery 

amoebic dysentery 

cholera Asiatica 

typhoid fever . 
Meconium 



infants 



tract 



221 

222 
222 
223 
223 
223 
223 
224 
225 
225 
226 
227 
227 
227 
228 
234 
235 
235 
237 
238 
238 
240 
240 
240 
240 
241 
242 
242 
242 



CHAPTER V. 

THE NASAL SECRETION. 



Definition 

The physiology and pathology of the nasal secretion 



244 
244 



CHAPTEE VI. 



THE SPUTUM 



Definition . . . 

General technique . 

General characteristics of the sput 

amount .... 

consistence 

color .... 

odor .... 

specific gravity 

configuration of sputum 
Macroscopic constituents of sputum 

elastic tissue . 

fibrinous casts 

Curschmann's spirals 

echinococcus membranes 

concretions 

foreign bodies 



245 
245 
246 
246 
247 
247 
248 
249 
249 
250 
250 
250 
252 
254 
254 
254 



CONTEST*. 



XV 



Mieroscopic examination 

leucocytes 

red blood-corpuscles 
epithelial cells 
elastic tissue . 
animal parasites 

tenia echinococcus 
distoma pulmonale 
vegetable parasites . 

pathogenic organisms 
the tubercle bacillus 

methods of staining 

Weigert-Ehrlich's method 
Gabett's method . 
Ziehl-Neelsen's method 
the diplococcus pneumoniae 
the bacillus of influenza . 
the bacillus of whooping-cough 
actinomycosis . 
non-pathogenic organisms 
crystals .... 

Charcot-Leyden's crystals 
haernatoidin 
cholesterin 
fatty-acid crystals 
leucin and tyrosin 
calcium oxalate 
triple phosphates 
Chemistry of the sputum 
The sputa in various diseases 
acute bronchitis 
chronic bronchitis . 
putrid bronchitis and pulmonary gangrene 
fibrinous bronchitis 
bronchial asthma . 
pulmonary abscess . 
abscess of the liver with perforation into the 
pneumonia 
phthisis pulmonalis 
oedema of the lungs 
heart-disease . 
the pneumoconioses 
anthracosis 
siderosis . 
chalicosis 
stycosis . 



PAGE 

264 

25 I 
255 



257 
258 

258 
259 
260 
260 
260 
262 
262 
262 
263 
263 
264 
264 
264 
265 
265 
265 
266 
266 
266 
267 
267 
267 
267 
268 
268 
268 
269 
269 
269 
269 
270 
270 
271 
271 
272 
272 
272 
272 
272 
272 



CHAPTER VII. 

THE URIXE. 



General considerations . 

General characteristics of the urine 

general appearance 

color .... 

odor .... 

consistence 

quantity .... 



274 
275 

27') 
27»; 
278 

27- 

27- 



XVI 



COX TEXTS. 



General characteristics of the urine— (hnUnued. 

polyuria ....•••••• 

oliguria 

specific gravity . . • • 

determination of the specific gravity ... 

determination of the solid constituents 

reaction 

determination of the acidity of the urine . 

The chemistry of the urine . . 

general chemical composition of the urine . 

quantitative estimation of the mineral ash of the urine 

the chlorides ........... 

test for the chlorides in the urine 

quantitative estimation of the chlorides by the method of Sal- 
kowski-Volhard 

direct method 

estimation of the chlorides alter incineration according to Neu- 

bauer and Salkowski 

the phosphates 

test for the phosphates in the urine ...... 

quantitative estimation of the total amount of phosphates 

separate estimation of the earthy and alkaline phosphates 

removal of the phosphates from the urine 
the sulphates 

tests for the sulphates in the urine .... 

quantitative estimation of the sulphates . 

quantitative estimation of the total sulphates . 
quantitative estimation of the conjugate sulphates 
urea 

properties of urea . 

separation of urea from the urine .... 

quantitative estimation of urea . . . . 

estimation of nitrogen according to Kjeldahl . 

estimation of nitrogen according to Will-Varrentrapp 
uric acid 

alloxur bodies 

properties of uric acid 

tests for uric acid .... 

quantitative estimation of uric acid . 
hippuric acid 

properties of hippuric acid 

quantitative estimation of hippuric acid 
kreatin and kreatinin .... 

properties of kreatin and kreatinin . 

test for kreatinin in the urine . 

quantitative estimation of kreatinin in the urine 
the xanthin bases 
the alloxur bases 



quantitative estimation 
oxalic acid 

properties of oxalic acid 

test for oxalic acid 

quantitative estimation of 
the albumins 

serum-albumin . 

serum-globulin . 

albumoses (peptones) . 

hsemofflobin 



oxalic acid 



PAGE 

279 

281 
282 
285 
287 
288 
292 
294 
294 
295 
296 
299 

299 
304 

305 
305 
311 
312 
315 
316 
316 
320 
321 
321 
322 
323 
332 
334 
336 
345 
347 
349 
353 
353 
355 
355 
362 
363 
364 
366 
366 
368 
368 
370 
371 
371 
373 
374 
375 
375 
376 
376 
389 
389 
391 



CONTENTS. 


xvii 




PAGE 


The chemistry Of the urine — Continued. 




fibrin 


. 893 


nucleo-albumin 


. 393 


histon ....... 


. 394 


tests for the albumins . 


. 395 


tests for serum-albumin 


. 396 


nitric-acid test .... 


. 396 


boiling-test 


. 399 


potassium ferrocyanide test 


. 400 


trichloracetic-acid test 


. 401 


picric- acid test .... 


. 401 


Spiegler's test .... 


. 402 


special test for serum-albumin 


. 402 


quantitative estimation of albumin . 


. 402 


old method of boiling . 


. 402 


volumetric method of Wassiliew 


.403 


Esbach's method 


. 403 


differential density method . 


. 404 


gravimetric method 


. 404 


test for serum-globulin and its quantitative 


5 estimation . 405 


tests for albumoses .... 


. 406 


tests for peptones .... 


. 406 


tests for (mucin) nucleo-albumin 


. 407 


tests for haemoglobin .... 


. 408 


Heller's test .... 


. 409 


the guaiacum test 


. 409 


test for fibrin 


. 409 


carbohydrates 


. 409 


glucose 


. 409 


tests for sugar 


. 415 


Trommer's test 


. 415 


Fehling's test 


. 416 


Bottger's test with Nylander's modificatio] 


i . .417 


fermentation-test .... 


. 417 


phenyl-hydrazin test .... 


. 418 


polarimetric test .... 


. 419 


quantitative estimation of sugar 


. 421 


Fehling's method .... 


. 421 


Knapp's method .... 


. 423 


differential density method 


. 424 


Einhorn's method .... 


. 425 


polarimetric method .... 


. 425 


lactose 


. 427 


levulose ....... 


. 428 


maltose . 


. 428 


dextrin 


. 428 


laiose 


. 428 


pentoses ....... 


. 428 


animal gum 


. 429 


inosit 


. 429 


urinary pigments and chromogens . 


. 429 


normal pigments ..... 


. 430 


urochrome ...... 


. 430 


uroerythrin 


. 431 


normal chromogens ..... 


. 132 


indican ...... 


. 132 


urohsematin 


. 436 


uroroseinogen ..... 


. !•">, 



XV111 



CONTENTS. 



The chemistry of the urine — Continued. 

pathologic pigments and chromogens 
blood-pigments 
hsematin 

urorubrohaematin and urofuscohsematin 
urohaematoporphyrin . 
biliary pigments . 
Smith's test . 
Huppert's test 
Gmelin's test, as modified by Eosenbach 
Gmelin's test 
biliary acids 
cholesterin . 
pathologic urobilin 
melanin and melanogen 
phenol urines 

alkapton .... 
blue urines .... 
green urines 

pigments referable to drugs 
Ehrlich's reaction 
conjugate sulphates . . 

skatoxyl ..... 
phenol and paracresol 
pyrocatechin .... 

acetone 

tests for acetone 
Legal' s test 
Lieben's test 
Eeynolds' test 
quantitative estimation 

diacetic acid 

oxybutyric acid .... 

lactic acid 
volatile fatty acids 
fat . m 
chyluria 
galaktosuria 
ferments . 
gases 

ptomains . 
Sediments 

Microscopic examination of the urine 
non-organized sediments . 

sediments occurring in acid urines 
uric acid .... 
amorphous urates 
calcium oxalate . 
ammonio-magnesium phosphate 
monocalcium phosphate 
neutral calcium phosphate . 
basic magnesium phosphate 
hippuric acid 
calcium sulphate 
cystin . 

leucin and tyrosin 
xanthin 
soaps of lime and magnesia 



438 
438 
438 
438 
438 
439 
441 
441 
441 
441 
442 
442 
442 
444 
445 
445 
446 
446 
447 
447 
452 
452 
452 
452 
452 
455 
455 
455 
455 
456 
457 
458 
458 
459 
459 
460 
460 
460 
461 
461 
462 
465 
465 
465 
465 
467 
468 
469 
470 
471 
471 
471 
472 
472 
474 
476 
477 





CONTENTS. 






xix 


PAGE 


icroscopic examination of the urine — Continued. 


bilirubin and ba?matoidin 177 


fat 






478 


sediments occurring in alkaline urine 






479 


basic phosphate of calcium and magnesium 






470 


ammonium urate 






479 


magnesium phosphate .... 






479 


ammonio-magnesium phosphate 






479 


calcium carbonate 






480 


indigo 






480 


organized constituents of urinary sediments . 






481 


epithelial cells 






481 


leucocytes . 








485 


red blood-corpuscles 








489 


tube-casts . 








492 


true casts 








493 


hyaline casts 








493 


waxy casts . 








497 


pseudo-casts 


. 






498 


cylindroids . 








498 


formation of tube-casts .... 






499 


clinical significance of tube-casts 






500 


spermatozoa 






503 


parasites 






504 


vegetable parasites 






504 


animal parasites 






509 


tumor particles 






510 


foreign bodies 









510 



CHAPTER VIII. 



TRANSUDATES AND EXUDATES. 



Definition 

Transudates 

general characteristics 
specific gravity . 
chemistry of transudates 
microscopic examination 

Exudates .... 
serous exudates 
hemorrhagic exudates 
tuberculosis 



cancer .... 
putrid exudates 
pus 

general characteristics of pus 
the chemistry of pus . 
microscopic examination of pus 

leucocytes . 

giant corpuscles . 

detritus 

red blood-corpuscles . 

pathogenic vegetable parasites 

protozoa 

vermes 

crystals 
chylous and chyloid exudates . 



511 
511 
511 
511 
513 
514 
514 
514 
515 
515 
515 
516 
516 
516 
516 
517 
517 
518 
518 
518 
518 
519 
519 
519 
519 



XX 



CONTENTS. 



CHAPTER IX. 

THE EXAMINATION OF CYSTIC CONTENTS. 



Cysts of the ovaries and their appendages 

Hydatid cysts _ ' 

Hydronephrosis 

Pancreatic cysts 



PAGE 

521 
523 
523 
523 



CHAPTER X. 



THE EXAMINATION OF CEBEBRO-SPINAL FLUID. 



Definition 
Amount . 
Appearance 
Specific gravity 
Reaction . 
Chemical composition 
Microscopic examination 
Bacteriology 



525 
526 
526 
528 
528 
528 
529 
529 



CHAPTER XI. 



THE SEMEN. 

Definition 

General characteristics .... 

The chemistry of the semen . 

The microscopic examination of the semen 

The pathology of the semen . 

The recognition of semen in stains 



531 
531 
531 
532 
532 
533 



CHAPTER XII. 



THE VAGINAL DISCHARGE. 



General description 

Bacteriology 

Vaginal bbennorrhcea 

Menstruation . 

The lochia 

Vulvitis and vaginitis 

Membranous dysmenorrhoea 

Cancer .... 

Gonorrhoea 

Abortion .... 



535 
535 
537 
537 
537 
538 
538 
539 
539 
539 



CHAPTER XIII. 

THE SECRETION OF THE MAMMARY GLANDS 

The secretion of milk in the newly born 

Colostrum 

The secretion of milk in the adult female 

Human milk 

The milk in disease .... 

determination of the specific gravity 

the estimation of fat 



541 
541 
542 
542 

544 
545 
546 



CLINICAL DIAGNOSIS. 



CHAPTER I. 

THE BLOOD. 

GENERAL CONSIDERATIONS. 

If blood be allowed to flow directly from an artery into a vessel 
surrounded by a freezing-mixture, and containing one-seventh of 
its own volume of a saturated solution of sodium sulphate, or a 
25 per cent, solution of magnesium sulphate (one volume to four 
volumes of blood), it will be observed that after some time a sedi- 
ment, presenting the ordinary color of arterial blood, has formed 
at the bottom, which is covered by a layer of clear, straw-colored 
fluid, the blood-plasma. 

Upon microscopic examination the sediment will be seen to con- 
tain: 

a. Xumerous homogeneous, non-nucleated, circular, biconcave 
disks. These measure on an average 7.5 p. in diameter, and are 
of a faint greenish -yellow color when viewed through the micro- 
scope, while en masse they present the color of arterial blood: the 
erythrocytes or red corpuscles of the blood. 

6. Roundish or irregularly shaped nucleated cells. These are 
far less numerous than the red corpuscles, and devoid of coloring- 
matter: the leucocytes, colorless or white corpuscles of the blood. 

c. Minute colorless disks, measuring less than one-half of the 
diameter of a red corpuscle: the so-called plaques, or blood-plates 
of Bizzozero. 

GENERAL CHARACTERISTICS OP THE BLOOD. 
The Color. 

Chemical examination of the blood has shown that its color is 
referable to the presence of an albuminous, iron-containing sub- 



18 CLINICAL DIAGNOSIS. 

stance, haemoglobin, contained in the bodies of the red corpuscles, 
which is characterized by its great avidity for oxygen, and forms a 
compound therewith, known as oxyhemoglobin. The relatively 
larger amount of the latter encountered in the arteries, as compared 
with the veins, causes the difference in the appearance of arterial 
and venous blood, the former presenting a bright scarlet-red, the 
latter a dark-bluish color. A bright cherry-red color of the blood 
is noted in cases of poisoning with carbon monoxide, while a 
brownish-red or chocolate color is observed in cases of poisoning 
with potassium chlorate, aniline, hydrocyanic acid, and nitrobenzol. 
A somewhat milky appearance is frequently seen in cases of well- 
marked leukaemia, and the author recalls an instance in which 
attention was first directed to the existence of this disease by the 
peculiarly milky appearance of a drop of blood obtained for the 
purpose of a haemoglobin estimation. In chlorosis and hydraemic 
conditions, as would be expected, the blood looks pale and watery. 

The Odor. 

The peculiar odor of the blood, which differs greatly in different 
animals, the halitus sanguinis of the ancients, is dependent upon the 
presence of certain volatile, fatty acids, and may be rendered more 
distinctly the addition of concentrated sulphuric acid. 

The Specific Gravity. 

The specific gravity of the blood in healthy adults varies between 
1.046 and 1.067, being higher on an average in men, 1.055, than 
in women, 1.054, and children— boys 1.052, girls 1.050. It is 
diminished to a certain extent by fasting, the ingestion of solids 
and liquids, gentle exercise, pregnancy, etc. The specific gravity, 
moreover, depends upon the bloodvessel from which the specimen 
is taken, being higher, generally speaking, in venous than in arte- 
rial blood. 

Under pathologic conditions the specific gravity may vary between 
1.025 and 1.068. In nephritis, chlorosis, the anaemias in general, 
as also in cachectic conditions (pulmonary phthisis, carcinoma of the 
stomach, etc.), it may diminish to 1.031. An increased specific 
gravity is met with in febrile diseases (typhoid fever 1.057 to 1.063), 
conditions associated with pronounced cyanosis (emphysema, fatty 



THE BLOOD. 19 

heart, uncompensated valvular disease, L.054 to L.068), and ob- 
structive jaundice, 1.062. 

Methods of Determining the Specific Gravity of the Blood. 

Roy's Method. A number of test-tubes are filled with a mix- 
ture of glycerine and water in different proportions, so that the spe- 
cific gravity in the different tubes shall vary between 1.025 and 
1.068. Blood is then drawn from the tip of a finger, or the lobe 
of the ear, into a capillary tube connected with an ordinary hypo- 
dermic syringe, pressure being carefully avoided. A drop of blood 
is placed in each tube, in which it will sink as long as the specific 
gravity of the glycerine mixture is lower than that of the blood, 
while it will remain suspended in a mixture the specific gravity of 
which is equivalent to its own. 

Roy states that it is important for the purpose of comparison to 
make such examinations in every case at the same hour, as the 
specific gravity of the blood has been shown to undergo diurnal 
variations. 

Hammersch lag's Method. A cylinder, measuring about 
10 cdi. in height, is partly filled with a mixture of chloroform 
(sp. gr. 1.526) and benzol (sp. gr. 0.889), presenting a specific 
gravity of 1.050 to 1.060. Into this solution a drop of blood is 
allowed to fall directly from the finger, pressure being avoided, 
and care being taken that it does not come in contact with the 
walls of the vessel. The drop, moreover, should not be too large, 
as it will otherwise separate into several droplets, giving rise to 
inaccurate results. Should the drop sink to the bottom, it is appa- 
rent that the specific gravity of the mixture is lower than that of 
the blood, necessitating the addition of more chloroform. This 
should be added, drop by drop, while the mixture is thoroughly 
stirred. If, ou the other hand, the drop of blood should tend 
toward the surface, it is best to add an amount of benzol sufficient 
to cause the blood to sink to the bottom, and then to bring it to the 
proper degree of suspension by the subsequent addition of chloro- 
form. As soon as the drop remains suspended the mixture is 
filtered, and its specific gravity ascertained by means of an accu- 
rate areometer, registered to the fourth decimal. The figure obtain d 
will express the specific gravity of the blood. 

The chloroform-benzol mixture may be kept indefinitely. 

With a little practice, results sufficiently accurate for clinical 



20 



CLINICAL DIAGNOSIS. 



purposes may thus be obtaiued with au expenditure of but very 
little time. 

Schmaltz a.\d Peiper' s Method. Where delicate scales are 
available the method of Schmaltz and Peiper may be employed, 
being the most accurate: A capillary tube, measuring about 12 em. 
iu length and 1.5 mm. in width, with its ends tapering to a diam- 
eter of 0.75 mm., is filled with blood and carefully weighed, wheu 
the weight of the blood, divided by the weight of an equivalent 
volume of distilled water, will indicate the specific gravity. 

Siegl and Schmaltz have shown that with the exception of hydre- 
mic conditions the specific gravity of the blood varies with the amount 
of hemoglobin. A simple method is thus given, by means of which 
hemoglobin estimations can be made in the absence of more expen- 
sive instruments, in the majority of cases. Cabot even prefers this 
method to the use of Fleischl's hemometer. In the following 
tables, which are taken from his work, 1 the varying degrees of spe- 
cific gravity, as obtained with Hammerschlag's method, and that 
of Schmaltz and Peiper, are given with the corresponding amounts 
of hemoglobin. The figures, however, are in all probability not 
quite accurate: 



Specific gravity 

according to 

Hammersehlag. 


Haemoglobin. 


Specific gravity 

according to 

Schmaltz and Peiper. 


Haemoglobin 


1.033-1.035 
1.035-1.038 


. 25-30 
. 30-35 


3er ct. 


1030 . 
1 035 . 


20 per ct. 

30 


1.038-1.040 


. 35-40 


" 


1.03S . 


35 


1.040-1.045 


. 40-45 


li 


1.041 . 


40 


1.045-1. 04S 


. 45-35 


« 


1.0425 . 


45 


1.048-1.030 


. 55-65 


i. 


1.0455 . 


50 


1.050-1.053 
1.053-1.055 
1.055-1.057 
1.057-1.060 


. 65-70 
. 70-75 

. 75-S5 
. 85-95 


a 
it 


1 048 . 
1049 . 
1.051 . 
1 052 . 
1 0535 . 
1.056 . 
1.0575 . 
1 059 . 


55 
60 
65 
70 

75 " 
. SO ' " 
90 
100 



Direct Estimation of the Solids of the Blood. Five 
drops of blood (0.2 to 0.3 gramme), obtained by means of a fairly 
deep incision, or puncture, into the tip of a finger, moderate pres- 
sure being made upon the middle phalanx, if necessary, are collected 



Clinical Examination of the Blood. Wm. Wood & Co. 



THE BLOOD. 21 

in a watch-crystal. This is at once covered with its fellow, the two 
being held together by means of a spring, and weighed. The speci- 
men (open) is then dried at a temperature of from 60° to 70° C. 
for twenty-four hours, and again weighed, the weight of the solids 
being thus ascertained. 

In healthy adults the following values were obtained by Stintzing 
and Gumprecht: 

Average. Maximum. Minimum. Average water. 

In men . . . 21.6 23.1 19 6 78.4 per cent. 

In women .19.8 21.5 18. 4 80.2 ■ " 

In conditions associated with chronic anaemia the solids, as would, 
be expected, are always considerably diminished. In leukaemia, on 
the other hand, owing to the large number of leucocytes present, a 
relative increase is observed. 

The Reaction. 

The reaction of the blood during life, owing to the presence of 
disodium phosphate, Na 2 HP0 4 , and sodium bicarbonate, NaHCO a , 
is alkaline, the degree of alkalinity in terms of sodium hydrate under 
normal conditions corresponding to 182 to 218 mgrms. for every 
100 c.c. of blood, v. Jaksch gives 260 to 300 mgrms. as the 
normal, and Canard 203 to 276 mgrms. 

The alkaline reaction of the blood may be demonstrated by re- 
peatedly drawing a strip of red litmus-paper, thoroughly moistened 
with a concentrated solution of common salt, through the blood, and 
rapidly washing off the corpuscles with the same solution, when, as 
a general rule, the alkaline reaction can be clearly made out. 

Small plates of plaster-of -Paris or clay, stained with neutral 
litmus-solution, may be similarly employed, the blood in this case 
being washed off with water. 

Generally speaking, the alkalinity of the blood is lower in women 
and childreu than in men, and is, furthermore, influenced by the 
process of digestion, exercise, etc. At the beginning of digestion, 
when hydrochloric acid is being secreted in large amounts, the alka- 
linity of the blood increases; while later on, when both hydrochloric 
acid and peptones are reabsorbed, the alkalinity in turn diminishes. 

A decrease is observed following violent muscular exercise, such 
as forced inarches in the case of soldiers, owing in all probability to 
an excessive production of acids in the muscles. 



22 CLINICAL DIAGNOSIS. 

Under pathologic conditions a diminished alkalinity of the blood 
is frequently observed, which is particularly marked in cases of 
pronounced anaemia (108 to 145 mgrms. of XaOH), increasing as 
the number of red corpuscles and the amount of haemoglobin 
diminish. In cases of chlorosis, however, the diminution in the 
number of red corpuscles is accompanied by a normal, or but 
slightly diminished alkalinity of the blood, as a whole. In leukae- 
mia, pernicious anaemia, nephritis when accompanied by uraemia, 
various hepatic diseases, diabetes, carcinoma, the various profound 
cachexiae, pseudo-leukaemia, poisoning with carbon monoxide, aud 
acids, and finally in high fever, as in typhoid fever, and toxic 
processes in general, the alkalinity of the blood is diminished, the 
lowest value found corresponding to 108 mgrms. of NaOH. A 
similar decrease follows the prolonged use of acids, while an in- 
crease is brought about by the ingestion of alkalies. An increase 
in the alkalinity of the blood occurs after a cold bath, and it is 
interesting to note that this is apparently associated with an increase 
in the bactericidal power of the blood. Possibly the beneficial 
effect of the cold baths in fever may be explained upon this basis. 

v. Jaksch employs the following method, a modification of that 
originally devised by Landois : Eighteen watch-crystals are pre- 
pared, each containing a mixture of a concentrated solution of 
sodium sulphate and a y^- and a yuuit norma l solution of tartaric 
acid in varying proportions, so that crystal 

No. C.c. C.c. 

I. Shall contain 0.9 of the 1/100 norm. sol. of the acid, and 0.1 of the cone. Na 2 S0 4 sol. 



II. 


0.8 


" 


" 0.2 


III. 


0.7 


« 


" 0.3 


IV. 


0.6 


" " " " 


" 0.4 


V. 


0.5 


" 


" 0.5 


VI. 


0.4 


" " " 


" 0.6 


VII. 


0.3 


" 


" 0.7 


VIII. 


0.2 


" 


" 0.8 


IX. 


0.1 


" " " " 


" 0.9 


X. 


0.9 


1 /iooo " " 


" 0.1 


XI. 


0.8 


" " 


" 0.2 


etc., for every c.c. 


of the mixture. 





Blood is taken, preferably from the back, by means of cupping- 
glasses, and, before it coagulates, 0.1 c.c. is added to every c.c. of 
the mixture described, when the reaction is determined in every 
crystal by means of very sensitive litmus-paper. The amount of 
acid contained in the specimen exhibiting a neutral reaction in terms 
of NaOH will then indicate the degree of alkalinity of the blood. 



THE BLOOD. 23 

As 150 (molecular weight) parts by weight of tartaric acid 
(C 4 H„0 6 ) combine with 80 (molecular weight) parts by weight of 
NaOH, or 75 with 40, according to the equation: 

^COOH XOONa 

(\,II.,(OH) ' + 2NaOH = C 2 H 2 'OH) 2 -f + 2H 2 

" x COOH x COONa 

a normal solution would contain 75 grammes of pure tartaric acid 
to the liter and a T \-$ and a yrr&TT normal solution, respectively, 0.75 
and 0.075 gramme. As 1000 c.c. of a y^- normal solution would 
correspond to 0.4 gramme of NaOH, and 1000 c.c. of a T1 yV<j- normal 
solution to 0.04 gramme, 1 c.c. of the T fa normal solution will 
represent 0.0004, and 1 c.c. of the 10 1 00 normal solution 0.00004 
gramme of NaOH. 

Supposing, then, a neutral reaction to have been obtained in 
the crystal containing 0.6 c.c. of the t ^q- normal solution, the alka- 
linity of the 0.1 c.c. of blood in terms of NaOH w r ould corre- 
spond to 0.00024 gramme of NaOH, or 0.24 gramme to 100 c.c. of 
blood 

As the alkalinity of the blood rapidly diminishes after being 
drawn, owing, in all probability, to the formation of an acid caused 
by the decomposition of the haemoglobin, it is apparent that the 
experiment must be performed as rapidly as possible, not more 
than one minute and a half being allowed to elapse between the 
taking of the blood and the conclusion of the experiment. 

This method has hitherto been the only one which was available 
for clinical purposes, and the results detailed above have been 
obtained by its aid. It is open to numerous objections, however, 
and still too complicated for routine work. Of late a new method, 
suggested by Lowy, has attracted much attention, and, to judge from 
the literature before us, is destined soon to replace the one described. 
It is both simpler and more accurate. The results, however, differ 
considerably from those given above, and a careful revision of all 
the work thus far accomplished with the old method will be neces- 
sary before definite conclusions can be reached. For the conveni- 
ence of future investigators a table is here appended containing 
some of the results which have already been obtained in some of 
the more important diseases. In healthy adults, while fasting, the 
alkalinity of the blood, according to Lowy's method, corresponds 
to about 300 to 325 mgrms. of sodium hydrate for every 100 c.c. of 
blood. Variations amounting to 75 mgrms. plus or minus, are, 



24 CLINICAL DIAGNOSIS. 

however, not uncommon, and, according to Strauss, the unavoid- 
able errors may correspoud to 30 mgrms. : 

Carcinoma oesophagi 227-643 

Carcinoma ventriculi 256-635 

Ulcus ventriculi . . . • • • • . • 302-460 

Anadeny of the stomach 354-360 

Alcoholic gastritis 343-3/9 

Chronic enteritis 212-272 

Phthisis pulmonalis 450-468 

Bronchitis 239-343 

Neurasthenia . . 225-426 

Arterio-sclerosis 208-344 

Chronic arthritis 368-465 

Erysipelas 498 

Typhoid fever 270-640 

Pneumonia 263-464 

Septicaemia 443 

Leukaemia 368-835 

Pernicious anaemia 429 

Diabetes mellitus 362-457 

Chronic interstitial nephritis 310-409 

Chronic parenchymatous nephritis . . . . 312-490 

Cirrhosis of the liver 272-345 

Lowy's Method. Five c.c. of blood obtained from one of 
the superficial veins of the arm (preferably the median cephalic) 
are allowed to flow into a small flask provided with a long and 
partially graduated neck and containing 45 c.c. of a 0.25 per 
cent, solution of ammonium oxalate. Coagulation is thus pre- 
vented and the blood made lake-colored — i. e., the haemoglobin 
is dissolved from the stroma of the red corpuscles. The mix- 
ture is then titrated with a -^V normal solution of tartaric acid 
with lacmoid paper soaked in a concentrated solution of magne- 
sium sulphate, as an indicator. The lacmoid paper is prepared as 
follows : 

A mixture of 100 grammes of resorcin, 5 grammes of sodium 
nitrite, and 5 c.c. of distilled water are heated on an oil-bath to a 
temperature of 110° C. A violent reaction occurs at this point, 
and the flame should be removed before this is reached. The sub- 
stance is then heated to a temperature of 115°-120° C. until all 
the ammonia which is evolved during the process has been driven 
off. The residue, which should be of a pure blue color, is dissolved 
in water and precipitated with hydrochloric acid. Upon cooling 
the coloring-matter is filtered off by the aid of a suction-pump, and 



THE BLOOD. 25 

washed with a little water. It is then dissolved in absolute alcohol, 
filtered, and the solution allowed to evaporate in an atmosphere 
free from ammonia. One gramme of the pigment, which crystallizes 
out in reddish-brown, glistening platelets, is dissolved in 1000 c.c. of 
45 per cent, alcohol, when strips of fine Swedish filter-paper are 
soaked in the solution and allowed to dry. 

As a normal solution of tartaric acid contains 75 grammes in the 
litre (see page 23), a -^ normal solution will contain 3 grammes, 
and 1 c.c. of the ^V normal solution will correspond to 0.0016 
gramme of sodium hydrate. 

Supposing, then, that 10 c.c. of the -£ s normal solution were 
necessary to neutralize the 5 c.c. of blood, the alkalinity of these 
5 c.c. in terms of sodium hydrate would correspond to 0.016 gramme, 
and the alkalinity of 100 c.c. of blood to 0.016 X 20 = 0.320 gramme 
— i. e., to 320 mgrms. 

CHEMICAL EXAMINATION OF THE BLOOD. 

General Chemistry of the Blood. 

A general idea of the chemical composition of the blood may be 
formed from the accompanying table of C. Schmidt, calculated for 
1000 parts: 





Man. 


Woman. 


Corpuscles 


. 5L3.0 1 


369.2 


Water 


. 349.7 


272.6 


Haemoglobin and globulins . 


. 159.6 


120.1 


Mineral salts 


3.7 


3.55 


Plasma ...... 


. 486.9 


603.8 


Water 


. 439.0 


552.0 


Fibrin 


3.9 


1.91 


Albumins and extractives 


. 39 9 


44.79 


Mineral salts 


4.14 


5.07 



If blood be allowed to flow into a vessel and set aside, it will be 
observed that at the expiration of a few minutes the entire mass has 
become transformed into a semi-solid, gelatinous material, which is 
spoken of as the blood-clot or the placenta sanguinis. Still later it 
will be seen that a small amount of straw-colored fluid has appeared 
on top of the clot, which gradually increases in amount, while the 
clot itself undergoes shrinkage, until finally the latter, greatly 

1 This figure is too high ; in man it varies between 420 and 470 for 1000 parts of blood. 



26 CLINICAL DIAGNOSIS. 

diminished in size, floats in the surrounding fluid. The straw- 
colored fluid which has thus been obtained during the process of 
coagulation is spoken of as the blood-serum. 

If, furthermore, a bit of the clot be examined microscopically, 
this will be seen to consist of a more or less dense network of 
fibres, the meshes of which are filled with blood-corpuscles, which 
may be washed out, leaving the fibrous network, fibrin, behind. 

Chemically speaking, fibrin belongs to the class of the so-called 
coagulated albumins, and probably does not occur in the circu- 
lating blood, but is formed only during the process of coagula- 
tion. 

The albumins which are found in plasma are fibrinogen, serum- 
globulin, and serum-albumin, and while serum-globulin and serum- 
albumin are likewise encountered in the serum, the fibrinogen has 
disappeared, and traces of a new albuminous body, fibrino-globulin, 
are found. There appears to be no doubt that fibrin results from 
the fibrinogen by a process of dissociation, traces of a soluble 
albumin, fibrino-globulin, being formed at the same time. Modern 
researches, furthermore, have shown that the transformation of 
fibrinogen into fibrin is dependent upon the action of a ferment, 
the fibrin-ferment, derived in all probability from the leucocytes of 
the blood by a process of plasmoschisis. The presence of serum- 
globulin apparently hastens coagulation in an indirect manner, as 
is done by calcium chloride and the calcium salts in general. 

Under normal conditions blood clots in from two to six minutes 
after being shed, while in disease, notably in haemophilia, coagula- 
tion may be greatly delayed, or even not occur at all, so that fatal 
hemorrhage may follow the infliction of trifling wounds. Whether 
or not this condition is referable to certain abnormalities in the 
chemical composition of the blood is as yet undetermined. 

A tendency to hemorrhage is also observed in scurvy, purpura, 
in some infectious diseases, such as typhoid fever, yellow fever, in 
poisoning with phosphorus, etc. 

Since the formation of fibrin begins as soon as the blood has left 
its natural channels, it is apparent that absolutely accurate an- 
alyses of blood-plasma can hardly be expected. The appended 
analyses of the plasma of the horse's blood are taken from 
Hoppe-Seyler and Hammarsteu, the figures having reference to 
1000 parts: 



THE BLOOD. 



27 



Water 

Solids 

Total albumins 

Fibrin 

Globulin 

Serum-albumin 

Fat . 

Extractives 

Soluble salts 

Insoluble salts 



908.4 
91.6 
77.6 
10.1 



1.2 

4.0 



( .)17.(i 



6.4 
1.7 j 



12.9 



The chief points of difference existing between plasma and serum 
are the absence of fibrinogen and the presence of traces of fibrino- 
globulin, as well as of large quantities of fibrin-ferment, in the 
latter. 

From the following table it will be seen that a marked difference 
exists in the nature of the mineral ingredients between serum and 
red corpuscles, the latter being relatively rich in potassium salts 
aud phosphorus, and poor in sodium salts and chlorine. 

The figures have reference to 1000 parts of blood : 



Man. 



Woman. 





Red 
corpuscles. 


Serum. 


Red 
corpuscles. 


Serum 


K. 2 . 


. 1.586 


0.153 


1.412 


0.200 


Xa,0 . 


. 0.241 


1.661 


0.64S 


1.916 


CaO . 










MgO - 










Fe 2 5 . 










CI 


. 0.898 


1.722 


0.362 


1.44 


PA • 


. 0.695 


0.071 


0.643 


2.202 



It is noteworthy that the amount of sodium chloride in the serum, 
6 to 7 p. m., remains fairly constant whether large amounts of 
sodium chloride are ingested or none given at all. It is quite 
probable that the sodium chloride of the plasma serves the pur- 
pose of preventing the haemoglobin of the corpuscles from being 
dissolved by the water of the blood. The term " isotonia " has 
been applied by Hamburger to a salt solution which is just strong 
enough to prevent the solvent action of the water upon the haemo- 
globin of the red corpuscles. In the case of the serum, however, 
we meet with a condition of hyperisotonia — i. e., an amount of salt 
in excess of that actually required in order to prevent the destruc- 
tion of the red corpuscles, the advantage of which is, of course, 
apparent, if the variations to which the amount of water in the 
blood is subject be borne in mind. 



98 CLINICAL DIAGNOSIS. 

In addition to the substances mentioned, the following are also 
found in the blood : 

Fat occurs in an amount varying from 1 to 7 p. m. in fasting 
animals, while following the ingestion of a meal rich in fats as 
much as 12.5 p. m. has been encountered. 

Soaps, cholesterin. and lecithin have likewise been found. 

Sugar, probably glucose, appears to form a normal constituent of 
the plasma, amounting to 1 to 1.5 p. m. in man. While it is pos- 
sible to increase this amount to a certain degree by the ingestion of 
large quantities of sugar, this appears in the urine, according to 
Claude Bernard, as soon as 3 p. m. has been exceeded. In addi- 
tion to glucose another reducing-substance has been found in the 
blood, which differs from the former in not being fermentable. 

Among the extractives which have been found there may be 
mentioned: urea, uric acid, kreatin, carbamic acid, sarco-lactic acid, 
glycogen, and hippuric acid, and under pathologic conditions xanthin, 
hypoxanthin, paraxanthin, adenine, guanine, leucin, tyrosin, lactic 
acid, cellulose, f 9-oxybutyric acid, acetone, and biliary constituents. 

It has been pointed out that the color of the blood is referable to 
the presence of haemoglobin contained in the red corpuscles, and 
also that the color varies from a bright scarlet-red in the arteries to 
a dark bluish-red in the veins, the exact shade depending upon the 
amount of oxygen present in combination with haemoglobin as 
oxyhemoglobin. Upon chemical examination two other gases may 
be demonstrated under physiologic conditions, viz., carbon dioxide 
and nitrogen. Of these the latter appears to play no part in the 
body-economy, and the amount present merely corresponds to that 
which would be absorbed by an equal volume of distilled water, 
viz., 1.8 vol. p. c, calculated at 0° C. and 760 Hgmm. pressure. 

The amount of oxygen and carbon dioxide, on the other hand, 
undergoes considerable variation, depending upon the particular 
bloodvessel from which the specimen is taken — i. e., whether this 
be an artery or a vein, and, furthermore, upon the velocity of the 
blood-current, the temperature of the body, rest, exercise, etc. 

The relation existing between the amounts of these gases in arte- 
ries and veins may be seen from the following table: 



Oxygen 

Carbon dioxide 
Nitrogen 



Arterial blood. 


Venous blood. 


21.6 per cent. 


6.8 per cent. 


40.3 


48.0 


1.8 


1.8 



THE BLOOD. 



2<) 



Oxygen, as already pointed out, occurs principally in chemical 
combination with haemoglobin (oxy haemoglobin), only 0.26 per 
cent, being present in solution in the plasma. 

Of the carbon dioxide which may be obtained from the blood, 
onlv one-tenth is held in solution, while the remaining portion is 
found in the red corpuscles, in the form of a loose compound with 
the alkalies of the corpuscles, and possibly also in combination with 
haemoglobin. This portion amounts to about one-third of the total 
quautity, while the remaining two-thirds are probably held in chem- 
ical combination by the alkalies of the plasma and certain albu- 
minous bodies. 

Blood-pigments. 

Hsemoglobin. Haemoglobin as such is found in only relatively 
small amounts in the circulating blood, occurring essentially in 
combination with oxygen as oxy haemoglobin, which predominates 
in arterial blood, while a mixture of oxyhemoglobin and haemo- 
globin is met with in venous blood, and haemoglobin almost exclu- 
sively in the blood of asphyxia. 



Cyanblue 




Spectrum of reduced haemoglobin, (v. Jaksch.) 



The spectrum of haemoglobin, in suitable dilution, shows one 
single band of absorption between D and E, which, however, does 
not lie midway between these lines, but extends slightly beyond D 
toward the left (Fig. 1). The substance is characterized by the 
ease with which it forms compounds with certain gases, and notably 
so with oxygen. As has been stated above, carbon dioxide also, to 
a certain extent at least, occurs in combination with haemoglobin. 
In cases of poisoning compounds of haemoglobin with carbon mon- 
oxide, with nitric oxide, and possibly also with sulphuretted hydro- 
gen, cyanogen, and acetylene have been observed. 

Oxy haemoglobin. Oxyhemoglobin is the most important con- 
stituent of the blood. In sufficiently dilute solution it shows two 



30 



CLINICAL DIAGNOSIS. 



bands of absorption between D and E ; one band, a, which is not 
so wide as the second, /?, but darker and more sharply defined, bor- 
ders upon D, while the second, which is wider, but less sharply 
denned, lies at E (Fig. 2). This spectrum can be readily trans- 
formed into that of hemoglobin by the addition of a reducing 
agent, such as an ammoniacal solution of ferrous tartrate (Stokes* 
fluid), ammonium sulphide, and cuprous salts. 




Spectrum of oxyhemoglobin, (v. Jaksch.) 



Under normal conditions the amount of oxyhemoglobin is fairly 
constant, but varies somewhat in different countries, in accordance 
with the habits of the people. Asa result of sixty-one estimations 
Leichtenstern found 14.16 per cent, as the average in healthy men, 
13.10 per cent, in women, and in old age about 95 to 115 per cent, 
of the normal. Among the inhabitants of the large cities of our 
country such excellent results are only exceptionally obtained, and 
in the writer's experience it is rare to find more than 13.01 per cent. 
As a general rule amounts varyiug between 10.96 and 12.33 per 
cent, are observed. This difference is undoubtedly owing to the 
fact that the average German spends very much more of his time 
outside the city-limits than the average American. Larger amounts 
are thus also found among the French and the English. 

While the ingestion of large amounts of water does not call forth 
a dilution of the blood and a diminution in the amount of oxyhe- 
moglobin, an increase occurs upon the withdrawal of liquids. Fat 
persons, furthermore, show a smaller amount of oxyhemoglobin 
than corresponds to their age. 

A great diminution in the amount of oxyhemoglobin may be 
encountered under pathologic conditions, and especially in chlorosis, 
while a relative increase is not infrequently met with in diabetes 
mellitus, owing to the excretion of abnormally large quantities of 
water. In nephritis with pronounced oedema it falls considerably 
below the normal. 



THE BLOOD. 



31 



In a series of observations Quincke found the following amounts 
in the diseases indicated: 







Fleischl. 


Angina pectoris . 


14.4 per cent. 


107.0 


Cerebral apoplexy 


. 14.1 


104.9 


Scurvy 


. 14.6 • " 


108.6 


Hepatic cirrhosis 


. 10.1 


75.1 


Chlorosis 


5.32-9.92 " 


39.5-73.9 


Splenic leukaemia 


. 5.8 


43.1 


Nephritis . 


8.5-10.7 


63.2- 79.6 


Diabetes 


14.4-15.9 


107.1-118.3 


Typhoid fever 


12.7-14.6 


94.4-108.6 


Recurrens . 


. 14.4 


107.0 


Meningitis . 


. 15.0 


111.6 


Pysemia 


. 11.3 


84.0 


Phosphorus-poisoning . 


. 14.9 


110.8 



In an analysis of 63 cases of chlorosis, observed at the Johns 
Hopkins Hospital, an average amount of 5.68 per cent. (42.3, 
Fleischl), with a minimum of 2.35 per cent. (17.5), was observed. 
Similar results were obtained by the writer in an analysis of 31 
cases. The average amount was 6.46 per cent. (42.8, Fleischl), 
and the lowest amount 2.46 per cent. (18, Fleischl). Chlorosis 
thus occupies the foremost position among the various pathologic 
conditions associated with oligochroinaemia. 

Yery low figures are also seen in cases of pernicious anaemia and 
leukaemia, where 2.68 per cent. (20, Fleischl) and 4.36 per cent. 
(32.5), respectively, were obtained. 

While in typhoid fever the amount of oxyhaemoglobin is always 
reduced, according to Osier, and usually in a greater relative pro- 
portion than the number of red corpuscles, the most severe grad( s 
of anaemia may here be encountered during convalescence, when 
the amount of oxyhemoglobin may fall as low as 2.68 per cent. 
(20, Fleischl). 

In the early stages of carcinoma of the stomach the cachexia is 
not well pronounced, and Schiile states that in his analysis of 198 
cases it only occurred in 30 per cent. This agrees entirely with 
the writer's experience, who repeatedly found amounts of haemo- 
globin exceeding 60 per cent. Later in the disease a most pro- 
nounced oligochromaemia is, however, invariably encountered. At 
this place the writer wishes to insist upon the importance of system- 
atically repeated examinations of the blood in all cases of suspected 



1 See estimation of haemoglobin with Fleischl's heemometer, p. 32. 



32 CLINICAL DIAGNOSIS. 

carcinoma of the stomach. A steady decline from week to week, 
when taken in conjunction with the other symptoms, and occurring 
in patients who have passed the fourth decade, is certainly very 
suspicious. 

A notable diminution in the amount of haemoglobin is further 
observed in tuberculosis, syphilis, chronic lead and mercurial poison- 
ing, chronic nephritis, chronic enteritis, etc. 

As the oxyhemoglobin is contained in the bodies of the red cor- 
puscles, it might be inferred that the amount of the former will 
directly depend upon the number of the latter, so that the degree 
of an anemia could be determined by an enumeration of the red 
corpuscles as well as by a direct estimation of the amount of oxy- 
hemoglobin. 

While this rule holds good generally, there are numerous excep- 
tions which go to show that a diminution in the amount of oxyhe- 
moglobin, viz., an oligochromcemia, is not necessarily accompanied by 
a corresponding diminution in the number of red corpuscles — i. e., 
an oligocythczmia. In chlorosis, for example, the red corpuscles 
may be present in normal numbers, while the amount of oxyhemo- 
globin is greatly diminished. Here, it is true, a well-defined oligo- 
cythemia simultaneously occurs in all severe cases, but even then 
the oligochromemia exceeds the oligocythemia. Conversely, in 
pernicious anemia the oligocythemia, while accompanied by an 
oligochromemia, quite constantly exceeds the latter. 

It is thus clear that definite inferences regarding the amount of 
hemoglobin cannot be drawn from an enumeration of the red cor- 
puscles, and vice versa. 

While it is generally possible to form a fairly clear idea of the 
degree of an anemia by inspection — i. e., by noting the " color" of 
a patient — it is a well-known fact that not every pale face denotes 
an anemic condition. Whenever special accuracy in examination 
or results for comparison are desired, recourse should hence be had 
to instruments especially devised for the purpose of determining- the 
amount of hemoglobin, known as hemoglobinometers or hemom- 
eters. 

Among these instruments that devised by Fleischl is undoubtedly 
the most convenient and has already largely replaced the older forms 
of Gowers, Malassez, and Hayem. 

Estimation of Hemoglobin with Fleischl' s H^emometer. 
The principle of the method depends upon the comparison of the 



THE BLOOD. 



33 



color of the blood, diluted with water, with that of a glass wedge 
stained with the golden purple of Cassius or a similar pigment. 

The instrument (Fig. 3) essentially consists of the glass wedge, a, 
just mentioned, to which a scale, b, is attached, ranging from to 
120, being placed at the thinnest, 120 at the thickest portion of 
the wedge. This, by means of a rack and pinion, can be made to 
slide from side to side beneath a platform corresponding to the stage 
of the microscope. In the centre of the platform there is a circular 



Fig. 3. 




v. Fleischl's haemometer. 



opening into which artificial light (daylight is not permissible) is 
projected from a circular plate of plaster-of-Paris, mounted beneath 
in the position of the mirror of a microscope. Into the circular 
opening a metallic tube, 1.5 cm. in height, closed at the bottom with 
a plate of glass, and divided into two equal compartments by a 
metal partition, is fixed. One compartment receives the light 
through the glass wedge, the red chamber, the other directly from 
the plaster-of-Paris reflector, the white chamber. 

3 



34 CLINICAL DIAGNOSIS. 

Capillary pipettes accompany the instrument and are of such a 
capacity that, if the blood of a perfectly normal individual be used, 
the mixture of blood and water, placed in the compartmeut receiv- 
ing light directly from the white plate, shall correspond in color to 
that derived from the colored wedge at the mark 100. The two 
compartments are partially filled with water, when the required 
amount of blood is obtained by placing one end of a capillary 
pipette in contact with a drop of blood obtained from the tip of 
a finger, or, still better, from the lobe of the ear that has been care- 
fully cleansed with Avater, alcohol, and finally with ether. The 
pipette is immersed in the white chamber and rotated between two 
fingers, when the blood will pass into the water, which dissolves out 
the haemoglobin from the corpuscles. Any trace of blood remain- 
ing in the pipette is carefully washed out with water, an ordinary 
medicine-dropper being used for the purpose. By means of the 
dropper the two compartments are then completely filled with water 
until a convex meniscus is obtained over the two chambers. A 
slip of paper is placed over the visible portion of the scale on the 
surface of the platform, immediately behind the well, c, and the 
glass wedge so adjusted by means of the screw that the color in the 
two chambers shall be the same. The number facing the notch in 
the scale-aperture of the platform will then indicate the percent- 
age of haemoglobin, that of a healthy individual corresponding to 
100. 

As the normal amount of haemoglobin contained in 100 grammes 
of blood is a little less than 14 grammes, the number 100 on the 
scale of FleischPs instrument corresponding to 13.7 per cent., the 
percentage in a given specimen may be calculated according to the 
equation: 100 : 13.7 : : p : x, and x = 0.137 p, where p represents 
the reading on the scale and x the corresponding amount of haemo- 
globin contained in 100 grammes of blood. 

According to Dehio, certain errors are incurred in the estimation 
of haemoglobin by means of FleischPs haemometer, which become 
the more marked the smaller the percentage. These may be obvi- 
ated, however, and accurate results obtained, as far as such is pos- 
sible, with the employment of colorimetric methods, if the instru- 
ment be previously tested with a solution of blood the color of 
which accurately coincides with that of the wedge at the 100 mark. 
To this end the standard solution is diluted with from 10 to 90 
volumes of water, and any difference that may exist in the read- 



THE BLOOD. 



35 



ings of the instrument, as compared with the known percentages, 
noted. 

If the number of red corpuscles be known, the amount of haemo- 
globin contained in each, " la valeur globulaire" of Lepinc, can 
now be readily determined, which is a point of considerable impor- 
tance in differential diagnosis. 

Estimation of Haemoglobin with Gowers' H^emoglobin- 
ometer. Gowers' haemoglobinometer is much cheaper than that 
of Fleischl and yields results which compare favorably with those 
obtained with that instrument. The apparatus (Fig. 4) consists of: 
a closed tube (D), containing a solution of picrocarmine-giycerine, 
the color of which corresponds to a 1 per cent, solution of normal 
blood; a similar tube (C), about 11 cm. in height, provided with an 
ascending scale of 134 divisions, each corresponding to 20 cbmm.; 
a capillary pipette (B), marked at 20 cbmm.; a guarded lancet (F); 
and a dropping-bottle with rubber top (A). 



Fig. 4. 






Cowers' hsemoglobinometer. 



In order to estimate the relative amount of haemoglobin in a given 
case the tip of a finger, or, still better, the lobe of the ear, is freely 
punctured, after having been carefully cleansed as described above, 
and the pipette filled with blood to the 20 cbmm. mark by suction. 
Any trace of blood that may adhere to the outer surface of the 
pipette is carefully wiped off, and the contents at once mixed with 
a few drops of distilled water, previously placed in the graduated 



36 CLINICAL DIAGNOSIS. 

tube, so as to guard agaiust the blood coagulating on its walls. In 
order to make the error incurred, when this method is employed, 
as small as possible, care should be had to remove completely every 
trace of blood from the interior of the pipette by refilling it with 
distilled water and blowing the contents into the graduated tube. 
The two tubes are then held side by side, directly against the light, 
or against a sheet of white paper, when water is added drop by drop, 
until the shade of color is the same in the two tubes. The division 
on the scale ultimately reached will express the relative percentage 
of haemoglobin. 

The method of estimating the amount of haemoglobin from the 
specific gravity of the blood has been described on page 20. 

H^emoglobin^emia. The term hemoglobinemia has been ap- 
plied to a condition in which, as the result of abnormal influences, 
the haemoglobin is dissolved out from the red corpuscles, and, 
appearing in the plasma as such, leads at first to a very decided 
choluria and in extreme cases to hemoglobinuria. 

Various poisons, such as potassium chlorate, carbolic acid, pyro- 
gallic acid, naphthol, arsenic, sulphide of antimony, hydrochloric 
acid, sulphuric acid, antifebrin, antipyrin, phenacetin, sulphonal, 
tincture of iodine, when given hypodermically, or even internally 
in sufficiently large doses, will call forth a hemoglobinemia, fol- 
lowed by hemoglobinuria. 

Fresh morels also contain a poison which is capable of producing an 
intense hemoglobinuria, and which may be extracted with hot water. 

In acute and chronic infectious diseases of a severe type, such as 
scarlatina, typhoid fever, intermittent fever, icterus gravis, syphilis, 
as also in diseases depending upon a hemorrhagic diathesis, such as 
variola hemorrhagica, scurvy, as also following insolation, extensive 
burns, and frostbite, hemoglobinemia, leading to hemoglobinuria, is 
not infrequently observed. 

An epidemic haemoglobin uria of the newly born and a paroxysmal 
or intermittent hemoglobinuria, both of unknown origin, have like- 
wise been described. 

In a case of Kaynaud's disease which the author had occasion to 
observe in the clinic of Dr. H. M. Thomas, at the Johns Hopkins 
Hospital, hemoglobinuria at times followed epileptiform seizures. 

Finally, hemoglobinemia followed by hemoglobinuria is observed 
after transfusion of the blood of one mammal into the circulation of 
another. 



THE BLOOD. 



37 



In some cases, and particularly in those following poisoning with 
chlorates, etc. , the haemoglobinaemia ultimately leads to a well-pro- 
nounced metha?moglobinaemia (see below). 

A haemoglobinaemia, aside from the urinary examination, may be 
readily recognized by a spectroscopic examination of the serum, 
when the two bands of absorption of oxyhemoglobin will be 
observed. 

A very simple method which may be employed for the same 
purpose is the following: A small amount of blood is drawn from 
the patient by means of cupping-glasses and immediately placed on 
ice, where it is allowed to remain for from twenty to twenty-four 
hours. At the expiration of this time the clot will have shrunk, 
floating, if the blood be normal, in the clear, straw-colored serum, 
while a beautiful ruby-red color is obtained in cases of haemoglo- 
binaernia. If, furthermore, some of this serum be heated to a tem- 
perature of from 70° to 80° C, the coagulum in the presence of 
haemoglobin will present a more or less deep brown color. 

Carbon Monoxide Haemoglobin. In cases of coal-gas poison- 
ing the blood, both of arteries and veins, presents a bright cherry- 
red color, owing to the presence of carbon monoxide haemoglobin. 

Such blood when properly diluted, like oxyhemoglobin, shows 
two bands of absorption between D and E (Fig. 5), which are 
nearer the violet end of the spectrum, however, and may be readily 



Fig. 5. 



Bed Orange 



Yellow 



Green 



Cyanblue 



A a 



B C 
40 50 

li ml nil Ini ill mini 



Eb 




30 90 .100 110 

IiiiiIiiiiIhiiIiiiiIiiiiIiiii 



Spectrum of carbon monoxide haemoglobin, (v. Jaksch.) 



distinguished from those referable to oxyhemoglobin by the addi- 
tion of a reducing agent. This will not affect the spectrum of 
carbon monoxide haemoglobin, while that of oxyhaemoglobin is 
transformed into the spectrum of reduced haemoglobin. 

For medico-legal purposes a number of additional tests have been 
devised, among which that suggested by Hoppe-Seyler is one of the 
simplest and at the same time most reliable. The blood is treated 
with double its own volume of a solution of sodium hydrate (sp. gr. 
1.3.). Normal blood is thus changed into a dirty-brownish mass, 



38 CLINICAL DIAGNOSIS. 

which, when spread out upon a porcelain plate, exhibits a trace of 
green, while carbon monoxide blood yields a beautiful red under 
the same conditions. 

Nitric Oxide Haemoglobin. The blood in cases of poisoning 
with nitric oxide, owing to the presence of nitric oxide haemoglobin, 
yields a spectrum which is similar to that of carbon monoxide 
haemoglobin, the bands, however, being less sharply defined and 
paler than those of the latter, and which, like these, do not disap- 
pear upon the addition of a reducing substance. 

Sulphuretted Hydrogen Haemoglobin (MethaemogvLobin Sul- 
phide). In cases of poisoning with sulphuretted hydrogen, not- 
withstanding the researches of Hoppe-Seyler, which go to show that 
haemoglobin will enter into combination with this gas, no definite 
changes can be discovered in the blood upon spectroscopic exami- 
nation. It is stated, however, that in such cases the blood becomes 
dark and of a dull greenish tint, the distinction between arterial 
and venous blood being at the same time lost. 

Carbon Dioxide Haemoglobin. With carbon dioxide, as men- 
tioned above, haemoglobin is also thought to enter into combination, 
the spectrum being similar to that of reduced haemoglobin. The 
latter, in fact, is formed artificially when carbon dioxide is passed 
through a solution of oxy haemoglobin. If this process be carried 
further, haemoglobin is decomposed, a precipitate of globulin being 
thrown down, and an absorption-band obtained which is similar to 
that resulting when haemoglobin is decomposed with acids (see 
below). The question has hence arisen whether the so-called carbon 
dioxide haemoglobin spectrum is not in reality referable to carbon 
monoxide haemochromogen, the haemochromogen, according to 
Hoppe-Seyler, being the colored portion of the haemoglobin and 
its compounds with gases. 

The blood-changes occurring in cases of poisoning with hydro- 
cyanic acid and acetylene are as yet but little known, and the reader 
is referred to special works upon toxicology for their consideration. 

Haematin. If haemoglobin in aqueous solution be heated to a 
temperature of from 60° to 70° C, it is decomposed into an albu- 
minous body, belonging, in all probability, to the class of globulins, 
and haematin. The same result is also reached by treating the 
aqueous solution with acids, alkalies, or the salts of various heavy 
metals. 

Haematin is an amorphous, blackish-brown or bluish-black sub- 



PLATE I. 



FIG. 1. 



& 



- als of Haemin. Highly magnified. 



FIG. 2. 



; "W au, -.u : 










»tals of Hasmatoidin from an Acholic Stool. 

s - 



THE BLOOD. 



39 



stance which is frequently encountered in old transudates, in the 
stools after hemorrhages, and after meals rich in meats — i. e., blood. 
It is said to occur in the urine in cases of poisoning with arsenic, 
and in the blood of animals poisoned with nitrobenzol the presence 
of this body is likewise said to be demonstrable with the spectro- 
scope. 

In acid solutions it shows a well-defined spectral band between 
C and D (Fig. 8). Between D and F a second band is seen, which 
is much wider, but less sharply defined than the first, and may be 
resolved into two bands by dilution, one between b and F, near F, 
and another between D and FJ, near E ; a fourth faint band, finally, 
may be obtained between D and E, near D. As a rule, only the 
baud between Q and D, and the broad band, viz., the two bands 
between D and F, are seen. 

In alkaline solutions, on the other hand, it shows but one broad 
band, the greater portion of which lies between C and D, extending 
slightly beyond D (Fig. 6). 

Fig. 6. 




Spectrum of hsematin in alkaline solution, (v. Jaksch.) 

If an alkaline solution of hrematin is treated with a reducing 
substance, reduced hsematin results, which gives rise to two bands 
of absorption between D and E (Fig. 7). 



Fig. 7. 



Yellow 



Green 



Cyanblue 




Spectrum of reduced haematin. (v. Jak&ch.j 



Hsemin. Haematin readily combines with one molecule of hydro- 
chloric acid to form hsemin. This substance crystallizes in light or 
dark brown rhombic plates or columns, w T hich are highly character- 
istic (Plate I., Fig. 1). They bear the name of their discoverer, 



40 CLINICAL DIAGNOSIS. 

Teichmann. The size of these crystals varies with the manner in 
which they are produced, the largest specimens being encountered 
when the glacial acetic acid (see below) is allowed to evaporate as 
slowly as possible. Specimens measuring from 15 fi to 18 ft in 
length may then be seen. Smaller crystals will be present at the 
same time, occurring either singly or gathered in stars, rosettes, and 
crosses. 

As these crystals may be obtained from mere traces of blood, 
their formation must be regarded as conclusive evidence in medico- 
legal examinations. Lewin and Rosenstein have pointed out, how- 
ever, that under certain conditions a negative result may be reached, 
even if the coloring-matter is derived from the blood. This is the 
case especially when the haemoglobin has been transformed into 
hsemochromogen or hsematoporphyrin, or when substances have 
been mixed with the blood which are either capable of altering its 
genera] composition or which, through their mere presence, inter- 
fere with the reaction itself. Such substances are certain salts of 
iron (rust), lead, mercury, and silver; further, lime, animal char- 
coal, and sand, when these are intimately mixed with the blood. 
In medico-legal cases a spectroscopic examination should hence also 
be made whenever the hsemin reaction is not obtained. 

Method. A small drop of normal salt-sol u tion is carefully evapor- 
ated upon a slide, when a few particles of the suspected material, 
powdered or teased as finely as possible, are placed upon the deli- 
cate layer of crystallized salt. The preparation is covered with a 
cover-glass, and glacial acetic acid allowed just to fill the space 
between the two glasses. The specimen is then carefully heated 
(three-quarters to one minute) until bubbles of gas begin to form 
beneath the cover. While evaporation is being continued glacial 
acetic acid is further added, drop by drop, from the edge of the slip, 
until a faint reddish-brown tint appears. As soon as this point is 
reached the last traces of the acid are allowed to evaporate, the 
specimen being held at a greater distance from the flame. A drop 
of glycerine is finally added, when the preparation may be exam- 
ined under the microscope, attention being directed especially to 
any reddish-brown streaks or specks, which, in the presence of 
blood, can usually be made out with the naked eye. 

Metheemoglobin. Methsemoglobin is a pigment closely related 
to oxyhemoglobin, and is frequently encountered in sanguinous 
transudates, cystic fluids, and in the urine in cases of hsematuria 



THE BLOOD. 



41 



and haenioglobinuria. In the circulating blood methaemoglobin is 
found after the ingestion of large quantities of potassium chlorate, 
notably so in children, as also after the inhalation of nitrite of 
amyl, the use of kairin, thallin, hydrochinon, pyrocatechin, iodine, 
bromine, turpentine, ether, perosmic acid, permanganate of potas- 
sium, and antifebrin. (See HaBmoglobinsemia, p. 36.) 

The spectrum of an aqueous or slightly acidified solution of methse- 
moglobin (Fig. 8) closely resembles that of an acid solution of haema- 
tin, but differs from the latter by the ease with which it is trans- 
formed into that of haemoglobin upon the addition of an alkali and 
a reducing substance. The spectrum of hsematin under the same 
conditions is transformed into that of an alkaline solution of baemo- 
chromogen. In alkaline solutions, on the other hand, two bands 
of absorption are observed, which are similar to those of oxyhemo- 
globin, but differ from these by the fact that the band nearer E, /?, 
is more pronounced than the one at D, a. A third, but very faint, 
band may further be observed between C and D, near _D. 



Fig. 



Bed Orange Yelloiv 

A a B C D 

10 50 60 70 

ml ii ni 



Green 
Eb 



Cyanblue 



80 90 100 110 



Spectrum of methsemoglobin in acid and neutral solutions, (v. Jaksch.) 

Hsematoidin. Small amorphous particles of an orange or ruby- 
red color, or crystals belonging to the rhombic system (Plate I., 
Fig. 2), occurring either singly or in groups, are frequently met 
with in the sputum, the urine, and the feces, as well as in old 
extravasations of blood. They were first discovered by Virchow, 
who applied the term haematoidin to this particular pigment, the 
hsemic origin of which is undoubted, being probably derived from 
hae matin. 

Hsematoporphyrin. Hsematoporphyrin is likewise a derivative 
of ha?matin, and, according to Nencki and Sieber, isomeric with 
bilirubin. In dilute solution with sodium carbonate it shows four 
bands of absorption, one between C and D, a second one, broader 
than the first, about D, especially marked between D and E, a third 
one, not so broad and less sharply defined between I) and E, and a 
fourth one, broad and dark, between b and F (Fig. 9). 






1LINICAJL BIAGWC ?ZS 



The clinical significance of this body, which also appears in the 
mine, as well as the causes giving rise to its formation, is as yet 
unknown. (See Hsematoporphvrinuria.) 



- r - 



A a B C 

m 

1 I 1 





7:> ; 



. 



C'i - : '■ -• 



z: 




While it is usually possible, as pointed out above, to recognize 
definitely the presence of blood by the hsemin-test, recourse should 
~ had to a spectroscopic examination whenever the exact 
natore of the pigment under consideration is to be determined. 



7::- :: 




~;^:~::; :;t 7i7i .ti: 



The Spectroscope. The spectr.; « »j ie Fig. 10 essentially con- 
dste ;.f a tube (A), provided with a slit at its distal end which may 
be'narrowed or widened, and a collecting-lens at its proximal end. 






THE BLOOD. 



43 



Through the latter rays of sunlight or of artificial light are thrown 
upon a prism (P), where they are decomposed into a colored spec- 
trum which is viewed through an astronomical telescope (B). 
Through a third tube (C) a fine scale, illuminated by artificial 
light, is reflected by the prism to the eye of the observer, appear- 
ing immediately above the colored spectrum, the left end of which 
is red, passing into yellow, this into green, then into blue, indigo, 
and finally into violet, which occupies the right end. These colors, 
however, are not continuous, but are interrupted by a large number 
of vertically placed dark lines, named after Frauenhofer. The 
most marked of these he designated by the letters: A, a, B, C, D, 
E, b, F, G, and H. Of these, A is found at the left end and B in 
the middle of the red portion of the spectrum, at the boundary of 
the red and the orange, D in the yellow, E in the green, F in the 
blue, G in the indigo, and H in the violet portion; a is situated in 
the red between A and B, nearer A, and b in the green between E 
and F, nearer E. (See Fig. 1.) 

If now a colored medium be placed between the slit and the light, 
not all the rays of colored light reach the eye, but some become 
absorbed. In the case of blood, for example, it may thus be seen 
that a portion of the yellow and a portion of the red rays are 
absorbed, a spectrum of this kind being spoken of as an absorption- 
spectrum. 

Fig. 11. 





Browning's spectroscope. (Zeiss.) 

For clinical purposes various instruments, modifications of the 
one described, have been devised, among which those of Desego of 
Heidelberg, Zeiss of Jena (Fig. 11), and Hoffmann of Paris, as well 
as Hering's lensless spectroscope, and Henocque's instrument, the 
latter two, owing to their cheapness particularly, deserve especial 
mention. 



44 



ciis'-iaz i-ia :-:' : >ii 



31: :_\ 



I~ :■■:-=: liriz:; zzi z: 
:: -".-—. :: ii :: t— ry 
:iiz_izz:::z in ::t:: z:z 
hyperalbuminagk and & 

:--•: ::-•::. zzi ::zzizr ii 
— izii '.::.— 7_ zr:zi 11 r -7- 
:": — :"-■'. in :;— : :_ : 
purgatives, etc. This ii 

~r.: : "r in : ZrrZi - . -i : ~t"t: 
:.-/-■■: - : - " - : 
minosis. on the other ban 

:.fi ii ::: : — zzi .::::. ii 
zi ± 1 :"-_. -t. -_r :'■ nzniri: 



Is of the blood from a clinical point 

:--:__ zis'z :-t:~~z :-z ::::tu ; - ;zz :: \ 
: 1: :z: ::z~zizz:iz^ :zr ::z:Iizi:z~ ;: 
bvminomz, respective!". As may be 

— iz'zz — i-fZr~rr ^.-v: is zi::t rzzin" 

zz:zz i: z z ' 7 ~ z :ii- _. : z : i- i.rZir 

/ zn i :: :ri: -: . : : il " ~z:z :zi z~- :: 

— :z :ir i— ziz: : zz:.ci::? is :z> z 

- lute increase has 

:T^::«:?;:r:. A: :■' - :iz:- ".-.7- z-i' :z- 

• s- : _ "r i :: ii ::: ". i r -:- : 1 i:«- :: ::> 

hemorrhage, dysentery, albominaria of 

i: r-i'-r : :>iiizzi: z~ : ' -. -::. Tzis is 

i'-rZLrTtiliy - : " ZZ Zr I ~nil J I ril" zi "i 1 .1 1 Z Z -r iz -Zr .: 11 Z1Z. Z ~ ZZ~Z 

— L «., a hydremia, which is particularly noticeable after hemor- 
rhages; and referable to a diminished secretion and excretion of 

- "-: l= ~-ii i.= :•: ; LizrZ. :' - z zi z :'z:z: :'zr : -- "-- 

Tlr rerni ;:_j-: ■: ;:•<■■* iizi ceen zzpiirl :: -i o 
amoont of fibrin is increased. T 
inflammatory diseases, such as pneumonia, pl< 
zz-zzzi:iszz ;z: .. r.-"-iv -ri: - ~izzir ; Lzzizi-z 
7.::::-:. zzi :--z :";i^:"r-i in zz :. i ;-. n ; . :: 
perzzzzzi zzznz: 

I- ::-ir: z: iiZi-zmiz- zir :z_ zz: :: z : :iz. i i :■: -iz :. ;. :■: :i :•:•::. 
obtained by means of cupping-glasses, are placed in a previously 
~ 't:^.-.t . :zz ::z:. — i:z ;z Izli;--rz': : rz ;.:■_-. :izr: r.^'zz :iir :-:::r 
- ~:::::,-i^ .1 7-^;- : -".:;'. r': :n. zrzz> :ir:i. Thr ii:-:; :- 
defibrinated by beating with the whalebone, when the beaker with 
--■= >:z:-z:i ;- " -._„ T _. :zf nrz::: in :I: :ir_n2 :lr ^ii^L: ;: :in 
blood. The-beaker is then filled with water and the mixture again 
beaten, whereupon the fibrin is allowed to settle; after being wa t 
~i"z ::-._.::. -:.:-vz:::_ i: ii zin:-i :zz; ;^z :■ zzLz-z :: kn:~n 
--- z z:z-: - ;-_r:. ~i:n z:;_;i -ni:-r :iz:i : _ zznl :zt :: : iz 
ooloring-matter, then boiled in alcohol to dissolve out the fat, choles- 
terin, and lecithin, dried at 110° to 120° C, and weighed upon 
cooling over sulphuric add. 

I:: --.zzzzii: . ■: :. - ~;.->;„ — .-• . ";i T -; i T z::z«:zz:- nzn- iz 
considerable quantities, and especially so after death, when the amount 



tion in which the 
occur in various 
: zilar 

imount of fibrin, 
tis, pyaemia, and 



THE BLOOD. 45 

progressively increased as decomposition advanced. Matthes, on 
the other hand, could detect no true peptones, but found that the 
blood contained a deuteroalbumose. In one case the serum con- 
tained an abundance of nucleoalbumin, derived in all probability 
from degenerated leucocytes. 

In order to test for peptones, all other proteids should first be 
removed, when a positive biuret-reaction in the filtrate will indicate 
their presence. 

Carbohydrates. 

Sugar. Sugar, as indicated above, occurs normally in the blood, 
its quantity varying between 1 and 1.5 p. m. Under pathologic 
conditions this amount may be exceeded by far, and notably so in 
diabetes, in which Hoppe-Seyler found as much as 9 p. m. in a 
certain case. 

In addition to sugar a non-fermentable reducing substance has 
been encountered in the blood, the exact nature of which is still 
unknown. 

Large quantities of a reducing substance, the greater portion of 
which consisted of sugar, have been met with by Trinkler in carci- 
noma; it was observed at the same time that carcinoma of the in- 
ternal organs was associated with far greater amounts of sugar 
than cancerous diseases of the skin and the mucous membranes. 
It is also interesting to note in this connection that an increase in 
the degree of the cachexia was not accompanied by an increase in 
the percentage of sugar. 

The results reached by Trinkler apparently also bear out the 
correctness of the conclusions formed by Freund, who claimed that 
a differential diagnosis between carcinoma and sarcoma, in which 
latter condition no increase in the amount of sugar was noted, can 
always be effected upon the basis of an examination of the blood 
in this direction. 

In the following table the percentages found in the different 
diseases investigated are given, from which it is apparent that next 
to carcinoma the largest quantities of sugar are met with in the in- 
fectious diseases and the lowest figures in diseases of the kidneys: 



4-: i\: ,1 zz± _-j~;5-~! 



_-;. i ::■: :'f--s: 



v.v 


■" : 


1 _:1 


,; 


0.0S13 


0.1092 


: :*> 


0.0796 


'•: : 


' ' 


0.Q6M 


--- 


m.mm 


0.0H0 


:•;-_- 


>of 


0.0350 


iL®$l? 


;.v 


O.OM9 


"i? 


O.OS3I 


0.03SL 


■; 




Ii rif: i: :-r~ : n -ir-iii ^2::: Zt :'.:o: "_ T : - V 
obtained by veiaesBetiiksra or cupping-glasses;,, are placed in an evapor- 
;-;i_-\:-_ 1 ::t":t- ~h ;,::. -■:.:. — r.__: : n--~ T':~if_'^i 
sodiiain sralplanfe and a few drops of aeettie acid. The mixture is 
:::i^i: :: :.l-. • :..i^-~ :::_: :. :. . jsiisel :_:::_•- 2 n :.=-li~ i~:-: i~ 
s:« 1 i= :^t :■:,•..:.. :i_ :_.> :e:vii^ . .:. .1 :i : ?-• i_- - "-/:-: i-iTir^ 
:erz :::7 ::c~> i.iiei :-: ic-e : ,.:i "/.z.iit. T_r iiliri:- :> 
passed thnoogh Swedish paper. In the final filtrat** the sugar is 
then esthnated as pointed out elsewhere. (See Urine.) 

Or the bleed is treated with four to five times its volume of 
Strang akU (9ft to 96 per cent.), s%hidhr 
aosL TV inixtture is allowed to stand far several 
being applied. It is then filtered and evaporated <o 
'-■.'.:._. :_-;'__ .,'.. -'.__- :.. 1 \ Li- -: z.^i :fi Slrcli i" :'"--~--v 
— ':.:•::- :: ::_:_ :..:« " : • -r— : -:--:;:-:- .'.^n.i r~::-..::--. "in 
alcohol. The final residue is dissolved in water. In this solniion 
'—- -":_•:: if '--::. e?r'-" -..ifi : . :■:■ i : :i._- : Kmi: ; i_ 7 :1 :•.:.. 

CM late Ckvaraani hasdiawn attention to another met* d I free- 
-- n- :.:•:•: :: — ; : mif "Li 1 .- - ' . ". - ■- -::.: \-r 1: :.-:: : : 77- 
and less expensive- To this end 2© to 30 ce. off blood are added 
to 100 ©.cl of distillled water in a porcelain dish and treated with 
fin^ or six drops of a solution consisting: of 10 parts of aeetie aod 
(sp. gr. 1.010) and 1 part of lactic add. The mixture is lboMfor 
■---■ * --~------ :-;-■; Lzi liif :.:..:;£ 111 -.-«:. r£ :-:-:: >•:>- 

~ - : - - ■ ~- '"--' iZ'-i ""■'■" " "1---T'" :: 11 2 
:-■- -"--- -:::•::-- ~ .: i .-- • ;■ -.■;.- -I rli 

" : '---- - - -i:.--"":.Ht ;i" : . i~ :::•:. :-t- :: :.i 

-;-:' ": - --'-:-'- :f 1: : , 1: ::*i :: m 7 ; 

-^•' -" -'■■."■ ■.■....;•:: "Jii.: i_7 i_..ni:- : e= 1:: 
-• - "■■•-- : i-7 1- •—,:'• : : :: : :i— -v —,>.'■= ; 
when coagulation will ©esmr at onee. On the 



Zl™ ; ". 1 


_i- 


— _ . 1 "•■ 


7 ~ : ~ 


. : 1. 1 _ 


- Irrl 


:; i : 1 


Li z z 


:i_ 1: 


: 1 .. ". 


: _i_ : : 


: ni~ 



THE BLOOD. 47 

at times be necessary to add a few more drops of the acetic acid 
solution. 

Glycogen. There appears to be no doubt that glycogen normally 
occurs in the blood of various animals. Huppert, in fact, succeeded 
in demonstrating its presence in all animals examined, the amount 
varying between 0.114 and 1.560 grammes for one hundred parts 
of blood. Czemy, on the other hand, was not able to confirm these 
results in the case of healthy adults, while in sick children an 
examination of the leucocytes furnished positive results, glycogen 
being met with — in chronic gastro-intestinal diseases, pneumonia, 
ansemia, furunculosis, cachectic conditions the result of tubercular 
disease, asphyxia, etc. In diabetes and leukaemia also the glycogen- 
reaction is said to be quite pronounced. 

Livierato, who recently investigated this question with great care, 
arrived at the following conclusions: 1. Glycogen is constantly 
present in the blood of healthy individuals; its presence, however, 
is confined to the blood-plasma. When present in increased 
amounts it also occurs in the leucocytes. 2. It is absent in cases 
of acute articular rheumatism and in inflammatory conditions of 
the serous membranes. 3. Increased amounts are found in acute 
croupous pneumonia, in typhoid fever, in phthisis, in the various 
exanthemata, etc. 4. In hepatic and cardiac diseases associated 
with effusion it is either absent or present only in traces. 5. An 
endoglobular reaction only may be obtained during the second half 
of the ninth month of pregnancy and during the first four or five 
days of the puerperal period. 6. The increase in the amount of 
glycogen is dependent upon the existence of an active local process, 
associated with fever, upon the formation of exudates containing 
peptonizable material, or upon the existence of a more or less 
pronounced hyperleucocytosis. 

In order to test for glycogen a drop of blood is carefully spread 
out between two cover-slips and dried at an ordinary temperature, 
when a drop of a solution composed of 1 gramme of iodine and 
3 grammes of potassium iodide in 100 grammes of concentrated 
mucilage is allowed to flow between the tw T o glasses. In the pres- 
ence of glycogen brown-colored granules will be observed occurring 
either free in the blood or contained in the so-called neutrophilic 
leucocytes. 

Cellulose. Cellulose has occasionally been found in the blood 
of tubercular patients. 



48 CLINICAL DIAGNOSIS. 

Urea. 

Urea normally occurs in the blood in traces — 0.016 to 0.020 per 
cent. — larger amounts being encountered whenever, for any reason, 
as in nephritis, various diseases of the urinary organs, cholera Asi- 
atica, cholera infantum, eclampsia, etc., its elimination is impeded, 
or whenever, as in fever, owing to increased albuminous decompo- 
sition, urea is formed in abnormally large quantities. 

In this connection it is interesting to note that a smaller amount 
of urea is found in fatal cases of eclampsia than in those ending in 
recovery, an observation which has been explained by the assump- 
tion that in this condition not only the kidneys, but also the liver, 
loses its functional activity. 

The methods which are available for the detection of urea in the 
blood are still too complicated for clinical purposes, and the value 
of the information derived so small as hardly to repay for the labor 
involved. Hoppe-Seyler' s method should be employed whenever 
an examination in this direction is deemed advisable. 1 

Uraemia. Formerly it was thought that the complex of symp- 
toms generally spoken of as uraemia was referable to the retention 
in the blood of urea or ammonium carbonate. This view has since 
been disproved, however, although it must be admitted that in 
uraemia an increased amount of urea is frequently noted. Other 
views, according to which uraemia is referable to an accumulation 
of potassium salts, of extractives, and especially of kreatinin, or of 
ptomaines in the blood, must still be regarded as being sub judice. 
There is no reason, however, to ascribe the uraemic condition to the 
retention in the blood of one particular constituent of the urine, and 
it is not at all improbable that a retention of all may be responsible 
for the symptoms observed. 

Uric Acid and the Xanthin-bases. 

Uric Acid. Formerly, the presence of appreciable amounts of 
uric acid in the blood was regarded as pathognomonic of gout. 

Since that time a definite lithaemia has been observed in a variety 
of disorders, however, such as pneumonia, acute and chronic neph- 
ritis, chronic gastritis, catarrhal angina, conditions associated with 

1 See Hoppe-Seyler : Handbuch der physiologisch- und pathologisch-chemischen Analyse. 
Vierte Auflage, p. 363. 



THE BLOOD. 49 

an insufficient aeration of the blood, as in various diseases of the 
heart, pleurisy with exudation, emphysema when accompanied by 
cyanosis, the severer forms of ansemia, etc. v. Jaksch claims to 
have found uric acid in the blood in 88.88 per cent, of his cases of 
nephritis. Fever in itself does not appear to lead to an increased 
production of uric acid, as negative results were obtained in nine 
cases of typhoid fever out of eleven, in five cases of acute articular 
rheumatism out of six, etc. The conclusion is thus forced upon us 
that the diminished alkalinity of the blood observed in nephritis 
and anaemia is, to some extent at least, dependent upon the pres- 
ence of a nitrogenous acid, while the diminished alkalinity of the 
blood observed in fevers is not referable to this cause. 

From a survey of the literature upon the subject it would 
appear that an increased elimination of uric acid in the urine is 
not necessarily accompanied by an increase in the amount of uric 
acid in the blood. Further researches in this direction are, how- 
ever, highly desirable, and particularly so in connection with the 
various forms of gastric disease, in which an increased elimination 
of uric acid, according to the author's experience, is so frequently 
observed. 

In order to test for uric acid in the blood the following method 
may be employed: 100 to 300 c.c. of blood, obtained by means of 
cupping-glasses, are at once diluted with three to four times their 
own volume of water and placed upon a water-bath. As soon as 
coagulation sets in a few drops of a 0.3 to 0.5 per cent, solution of 
acetic acid are added until a feebly acid reaction is obtained. After 
having been kept upon the boiling-water bath for from fifteen to 
twenty minutes longer, until the albumin has separated out and 
settled in brownish flakes, the mixture is filtered while hot and 
the precipitate washed repeatedly with hot Avater. Filtrate and 
washings, which usually present a slightly yellow or brownish 
color, are again brought to the boiling-point after the addition of 
0.3 to 0.5 per cent, of acetic acid, decanted, filtered, and after the 
addition of a small amount of disodic phosphate further treated 
according to the Ludwig-Salkowsky method (see Urine). The first 
filtrate is then treated with hydrochloric acid, evaporated to about 
10 c.c, and allowed to stand for twenty-four hours, when the uric 
acid that has separated out is filtered off through asbestos or glass- 
wool. The filtrate may then be examined for xanthin-bases accord- 
ing to the same method. If no uric acid crystallizes out, as not 

4 



50 CLINICAL DIAGNOSIS. 

infrequently occurs, the acid fluid is directly examined for uric acid 
by means of the murexide-test (which see). If, upon the addition 
of ammonia, no distinct red color develops, the residue, after thor- 
ough desiccation, is dissolved in water, when a reddish color may 
be regarded as indicating the presence of nric acid, while a yellow 
or brown color is referable to certain xanthin-bases. Hopkins' 
method may also be employed. 

G-arrod's Test : This test may be advantageously employed if it 
be merely desired to determine whether or not large amounts of 
uric acid are present in the blood. A few c.c. of blood-serum (5-10) 
or of serous fluid, obtained by means of a blister, are placed in a 
watch-crystal and treated with from 6 to 10 drops of a 30 per cent, 
solution of acetic acid. A thread of linen is immersed in the fluid, 
which is then kept at a low temperature for from twelve to twenty- 
four hours. At the expiration of this time a few uric-acid crystals 
will have separated out upon the thread if the substance be present 
in large amounts. The true nature of these crystals may then be 
further determined by the microscope and the murexide-test. (See 
Uric Acid in the Urine.) 

Xanthin-bases. Xanthin-bases, as pointed out before, do not 
occur in normal blood, but have been encountered under pathologic 
conditions, as in typhoid fever, lymphatic tuberculosis, emphysema, 
phthisis pulmonalis, pleurisy, and chronic nephritis. 

The method above indicated for the demonstration of uric acid 
in the blood should also be employed when it is found desirable to 
test for these bodies. (See Urine.) 

Fat and Fatty Acids. 

An increase in the amount of fat normally present in the blood, 
aside from that arising after the ingestion of large amounts of fatty 
food, is met with in cases of obesity, chronic alcoholism, injuries 
affecting the long bones, as also in severe cases of diabetes, various 
hepatic diseases, chronic nephritis, tuberculosis, malaria, cholera, 
etc. This increase constitutes the condition spoken of as lipcemia. 
The term lipacid<xmia has been applied to the occurrence of volatile 
fatty acids in the blood, noted by v. Jaksch in various febrile dis- 
eases, leukseniia, and at times in diabetes, in which this condition is 
supposed to stand in a causative relation to the coma. /9-oxybutyric 
acid has been found post mortem in the blood in diabetes. 



THE BLOOD. 51 

To test for fat in the blood it is only necessary to examine a drop 
microscopically for the presence of minute, highly refractive globules 
which are readily soluble in ether. 

To test for fatty acids 20 to 30 c.c. of blood, obtained by means 
of cupping-glasses, are treated with an equivalent weight of sodium 
sulphate and boiled. The filtrate is then evaporated to dryness and 
extracted with absolute alcohol. Upon evaporation of this solution 
fatty acid crystals will be obtained, which can be readily recognized 
with the microscope. (See Feces.) 

Lactic Acid. 

There appears to be some doubt whether or not lactic acid nor- 
mally occurs in the blood of man during life, while after death its 
presence appears to be constant, the amount determined as zinc 
lactate varying between 0.233 and 6.575 p. m. In the series of 
cases studied by Irisawa it was impossible to account for the great 
variations observed in the amount of lactic acid by the character 
of the disease causing the fatal termination, and it is possible that 
the cause therefore lies in the fact that in some cases the blood was 
obtained shortly after death, while in others many hours had 
elapsed, as Irisawa himself suggests. 

The method employed by him is the following: 100 to 300 c.c. 
of blood are extracted with three times their own volume of alcohol, 
filtered, and the filtrate evaporated to a syrupy consistence. This 
is then made strongly alkaline with barium hydrate and shaken 
with large quantities of ether, in order to remove the fats present. 
The residue is acidified with phosphoric acid and again shaken with 
ether for twenty minutes at a time, until the process has been re- 
peated five or six times, the lactic acid passing over into the ether. 
The ether is distilled off from the extract, the residue taken up with 
water, and the solution carefully evaporated in order to drive off 
any ether still remaining, as well as the fatty acids. Carbonate of 
zinc is now added and the solution heated to 100° C. and filtered. 
The filtrate is evaporated on a water-bath until crystallization be- 
gins, when it is allowed to cool £nd treated with a few drops of 
absolute alcohol, in order to effect a complete separation of the 
lactate of zinc. The solution is allowed to stand exposed to the 
air until a constant weight is obtained. 

From the blood of living dogs Irisawa was able to obtain lactic 



-_ CLiyiCAL DIAGNOSES. 

acid in every Jase, and it was observed, moreover, that the amount 
found stood in direct relation to the degree of antenna produced. 

Biliary Constituents. 

Biliary constituents — i. e. . bile-pigment and biliary acids — are not 
encountered in the blood under normal conditions, bur are found 
whenever they are present in the urine (which see . It is note- 
worthy, furthermore, that bilirubin may frequently be demonstrated 
in the blood when a urinary examination in this direction yields 
negative results, and. ing to v. Jaksch, bilirubin occurs in 

the blood in nearly every ease in which urobilin exists in the urine, 
showing that bile-pigment circulating in the blood is. in all proba- 
bility, transformed into urobilin in the kidneys. 

A :holcemia is encountered in various pathologic conditions ass - 
dated with a resorption of bile from the biliary passages, as in 

-Tractive jaundice, an ext ssive elimination of bile into the intes- 
tinal canal, as well as with an increased destruction of red corpuscles. 

In order to test for biliary acids in the blood, the presence of 
which leads to destruction of the red corpuscles, as well as to the 
Jatory disturbances so constantly encountered, the blood is first 
treated with alcohol, in order to remove the proteids. The biliary 
acids which are present in the filtrate are next transformed into 
their lead salts by means of acetate of lead and ammonia, and 
thus precipitated. .liter washing with water the precipitate is 
boiled witL alcohol and filtered. The lead salts are decomposed 
by means of sodium carbonate, the solution is again filtered, the 
filtrate evaporated to dryness, and the residue extracted with abso- 
lute alcohol. The alcohol is distilled off, when the biliary salts of 
sodium will crystallize out or remain behind as an amorphous 
mass, which may be bested directly according to Pettenkofers 
method. To this end some of the residue is dissolved in water and 
with two-thirls of its volume of concentrated sulphuric 
acid, care being taken that the temperature does not rise beyond 
To this mixture a few drops of a i ) per cent, solution of 
cane-sugar are added, when in the presence of biliary acids a beau- 
tiful violet color is obtained. ^\hich is referable to the action of 
furfurol, formed from the cane-sugar and the acid, upon the biliary 

Bilirubin can be demonstrated in the blood most readily in the 



F LATE -- 

FIG 

<5£ 



.#"• 



Z . t . t - - :--*: ' ~- 



' 1 § 



- - : 1 : 

; : i - - - - - : '■>'■ " ' '- - - r ~— - ----- 



O T „a* 

°00° o° 




5 o v ~~o 



OS? >&»«». 



Tine Tasiknis EBetnraeflHHs <off ttfiae Btoswfi SOaBHneai weBSii E&urfliieaa''s 



- ; - - I " 



THE BLOOD. 53 

following manner: 10 to 15 c.c. of Mood, obtained by means of 
cupping-glasses, arc allowed to coagulate, when the scrum is re- 
moved by means of a pipette, filtered through asbestos, and coagu- 
lated in as thin a layer as possible, at a temperature of 80° C. 
Under such conditions normal serum will present a light straw 
color, while in the presence of biliary coloring-matter a light- 
greenish color is obtained, which becomes grass-green on standing. 
Should the serum contain haemoglobin, as in cases of haemoglobin- 
semia, a brownish color results. 

Acetone. 

Acetone has been found in considerable amounts in the blood 
under various pathologic conditions, and especially in fevers. 

In order to demonstrate the presence of acetone in the blood this 
is first extracted with ether and subsequently distilled, when the 
distillate is tested as indicated elsewhere. (See Acetonuria.) 



MICROSCOPIC EXAMINATION OF THE BLOOD. 

The Red Corpuscles. 

Variations in the Size of the Red Corpuscles. If a drop of 
blood, most readily obtained from the tip of a finger or the lobe 
of the ear, be examined with the microscope, a large number of 
faintly yellow, non-nucleated, circular, biconcave disks will be ob- 
served: the red corpuscles, or erythrocytes of the blood (Plate II., 
Fig. 1, a). 

Under normal conditions variations in the size of the red corpuscles 
are observed, and Hayem distinguishes between corpuscles of aver- 
age size, measuring from 7.2 p. to 7.8 p. in diameter, small corpuscles, 
presenting an average diameter of from 6 ti to 6.5 ft, and large cor- 
puscles, measuring from 8.5 )jl to 9 11. 

In certain diseases which are accompanied by a marked oligo- 
cythemia both abnormally small and large corpuscles arc encoun- 
tered, which have been termed microcytes and macrocytes, respec- 
tively. The former measure from 3.5 fi to 6 //, the latter from 
9.5 a to 12 a in diameter. Still larger forms, the megalocytes, or 
giant corpuscles of Hayem, are also at times seen in which the 
diameter measures from 10 fi to 16 n. These latter arc of consid- 



54 CLINICAL DIAGNOSIS. 

erable importance, as their presence in large numbers appears to 
be confined almost entirely to the blood of pernicious anaemia. In 
chlorosis they are far less common. 

The terms microcythoeinia and macrocythcemia have been applied 
to conditions in which the smaller or the larger forms, respectively, 
predominate in the blood. While there appears to be no doubt 
that a true macrocythsemia exists in the circulating blood in various 
forms of anaemia, and while microcytes also may occur, as such, in 
the circulating blood, the latter are only exceptionally met with, 
the ordinary inicrocytbaemic condition, according to Hayem, being 
artificially produced during the preparation of the specimen, so that 
this term really conveys a wrong impression, and should be dis- 
carded. Although admitting the correctness of Hayem' s view to 
a certain degree, there can be no doubt that, under pathologic con- 
ditions, abnormally small red corpuscles are quite constantly met 
with in large numbers, be they pre-existent, as such, in the circu- 
lating blood, or produced artificially during the preparation of the 
specimen. They are thus seen accompanying the condition of 
macrocythaemia, in pernicious anaemia, leukaemia, the pseudo-leukae- 
mic condition of children, the various severe anaemias in general, 
and even in chlorosis. 

Variations in the Form of the Red Corpuscles. Going hand 
in hand with variations in the size of the red corpuscles there are 
variations in form, and both microcytes and macrocytes. particu- 
larly the latter, generally do not present the normal circular appear- 
ance, but abnormalities in form, noted in connection with those of 
normal size (Plate II., Fig. 1, 6). Corpuscles are thus seen which 
resemble a flask, a kidney, a biscuit, an anvil, etc., while others, 
again, present such irregularities in form that it is impossible to 
compare them with any known object. 

The term poikilocytosis has been applied to alterations both in the 
size and in the form of the red corpuscles. This condition may be 
observed in the various forms of anaemia, and is especially pro- 
nounced in pernicious anaemia, of which disease it was once 
thought to be pathognomonic. In chlorosis, poikilocytosis is 
usually only seen in the most severe cases, and particularly in 
those manifesting a tendency toward thrombosis and embolism. 

Variations in the Number of the Red Corpuscles. The 
number of red corpuscles in the blood of healthy individuals is 
fairly constant, and the statement generally found in text-books 



THE BLOOD. ;,;, 

that 5,000,000 to 5,500,000 are contained in every cbmm. of blood 
in the adult male and 4,500,000 in the adult female la fairly 
accurate. 

An increase in the number of red corpuscles is noted almoel 
exclusively in conditions associated with a loss of large quantities 
of fluid from the body. It is thus especially encountered in the 
so-called algid state of cholera Asiatica, where from 6,200,000 to 
6,500,000 may he found in the cbmm. In the ordinary forms of 
severe diarrhoea an increase of 1,500,000 is also by no means rare. 
An increase is further observed in diabetes, but is not dependent 
upon a concentration of the blood, as it may also be seen follow- 
ing au increased ingestion of fluids as well as while fasting. While 
there can thus be no doubt that a polycythemia does occur, experi- 
ments have demonstrated almost exclusively that such a condition 
does not exist in what is generally spoken of as true plethora, and 
that the various symptoms of plethora, formerly attributed to an 
increase in the total amount of blood or of the red corpuscles, are 
referable, more likely, to vasomotor disturbances. 

A diminution in the number of red corpuscles, on the other hand, 
is frequently observed; it may be temporary, when following hemor- 
rhages, for example, or permanent. An oligocythemia is observed 
in various forms of anaemia, of whatever origin, and the number may 
fall to 360,000, and even lower in fatal cases. In pernicious anae- 
mia the lowest figures have been noted, and Quincke cites a case in 
which just before death only 143,000 red corpuscles were counted 
in the cbmm. 

When the anaemia is progressive the body apparently becomes 
habituated to the diminution in the number of red corpuscles, and 
it is surprising to find individuals attending to the duties of every- 
day life with a blood-count of only 2,000,000, or even less. It is 
not uncommon even to meet with cases of pernicious . anaemia in 
hospitals in which the patients with only 500,000 corpuscles are 
not obliged to go to bed. Nevertheless it must be admitted that, 
whenever the number falls beneath this figure, recovery' is prob- 
ably out of the question. A sudden reduction in their number to 
1,000,000, moreover, is usually followed by a fatal result. 

Very important is the fact that in acute gastritis and usually 
in chronic gastritis also the number of red corpuscles is not dimin- 
ished, while in cases of carcinoma a marked oligocythemia exists. 
In the severer forms of chronic gastritis a diminution is fairly eon- 



56 CLINICAL DIAGNOSIS 

slant, but rarely so marked as in carcinoma, if we except those 
ases of gastric anadeny. which present the clinical picture of a 
pernicious anaemia. In ulcer of the stomach normal values are 
found unless haeniateinesis has recently occurred or unless the dis- 
jase is associated with profound chlorosis. 

Nucleated Red Corpuscles. Two varieties of nucleated red 
corpuscles may be seen: 

1. Normoblasts: These are nucleated red corpuscles of the size 

:.rv erythrocyte, and appear to be identical with those 
normally found in the bone-marrow of adults. The nucleus of 
normoblasts, which frequently shows signs of undergoing division, 
is usually situated centrally, although an eccentric position also is not 
infrequently t>bs srve :1. These forms are further characterized by the 
great avidity with which their nuclei take up stains i Plate EL, Fig. 2). 
Tree nuclei, undoubtedly derived from the normoblasts, may also 
be met with in the blood. 

2. Mesraloblasts. or crisrantoblasts of Ehrlich: These elements are 
from three to live times as large as a normal erythrocyte, and are 
provided with a large nucleus, which, according to Ehrlich. never 
manifests signs of undergoing division, however, and is rarely 
stained as deeply as the normoblastic nucleus (Plate II.. Fig. 2). 
As the megaloblasts are normally met with only in foetal bone- 
marrow, Ehrlich views their presence in the blood of adults as a 
symptom of degenerative metamorphosis. Their presence in the 
blood in the absence of normoblasts he furthermore regards as a very 
grave symptom. Recently, however. Askanazy has reported a case 
of bothriocephalus anaemia in which megaloblasts in large numbers. 
but scarcely any normoblasts, could be discovered, and in which 
the patient recovered completely after the expulsion of sixty-seven 
parasites. The same observer also noted that the nuclei of megal- 
oblasts may undergo indirect division, and that the nuclei of normo- 
blasts frequently present the picture of karyorhexis. He concludes 
that a material difference does not exist between normoblasts and 
megaloblasts, and that the former develop from the latter. 

Megaloblasts are especially numerous in pernicious anaemia and 
leukaemia, while in the so-called secondarv anaemias they occur in 
only small numbers and are at the same time much degenerated. 
As a rule, nucleated red corpuscles cannot be made out in fresh 
3, and it is generally necessary to stain the blood accord- 
ing to special methods (see p. 



THE BLOOD. 



57 



The Leucocytes. 

The leucocytes, or colorless corpuscles of the blood, as seen in 
freshly prepared specimens, are roundish or irregularly shaped cells, 
being mostly larger than the red corpuscles; they are nucleated, and 
many are distinctly granular in appearance, so much so, in fact, that 
the nuclei are often entirely hidden from view (Plate II., Fig. 1, a). 
In a carefully prepared specimen some leucocytes will be met with 
which are endowed with the power of locomotion, creeping over 
the field of the microscope by throwing out pseudopodia in a manner 



Fig. 12. 




Phagocytosis. 



analogous to that seen in amoebae. In their general mode of living 
these motile leucocytes, moreover, closely resemble the latter organ- 
isms, and it is most interesting to observe the manner in which 
these little bodies take up cellular debris, and even obnoxious 
organisms that may be present in the blood. In malarial blood, 
for example, in which, as will be shown more particularly later on, 
certain amoebic parasites are present, one is not infrequently able to 



- ; CLLSJICAL BIAGWOSIS. 

observe leucocytes approach these bodies and take them ap by 
flowing around them, as it were (Fig. 12). Metschnikoff even 
regards this f onetion of the leucocytes as their most important one. 

Z'zz :-t \-zz.z-~ ~'iLZ- ' .:v:v ZzZz-. y~-z :: r-rin : Tin;: :::t:^i. 
mm:-: :: : :_ :i- :.:•:. -i:.^T :ri :-:i:r . :L^or:^ ":j mis 
observer; and, according to his views, the outcome of a bacterial 
invasion of the body, figuratively speaking, will depend upon the 
superiority of the organisms engaged in warfare. The term phago- 
eghms has been applied to the destruction of bacteria by leucocytes. 

Variations in the Number of the Leucocytes. While the 
number of red corpuscles is subject to very slight variations under 
physiologic conditions, that of the leucocytes varies within fairly 
wide limits, being influenced by the age and sex of the individual, 
pregnancy, the process of digestion, the character of the bloodvessel 
zz-.ZL — ii:_ zl~ sieiiziri i~ :,i£ri. -::. 

According to Osier, the number of leucocytes per cbmm. of blood, 
obtained from the linger or the ear, normally varies between 5000 
and 7000, so that taking 5,000,000 as the average number of red 
corpuscles per cbmm., the ratio between the two would vary between 
1 : 714 and 1 : 1000. 

1- ~:ii :i : -ziZZrZ zzzzzzzZ.-rZ :: '.- . :: :;: — is £: m i. ;. ::: :i::m :: 
IZ iis:n:i:. :mi in zzi^zl. ~niir ZLz,j-zl ~ .is v._: :\- :: :isirv- iij 

^LZtI'tL:-:, 

An increase in the number of leucocytes, to which condition the 

~ : : - — .-: . " " .: -_ . :~~ r::;i;-~. is z.^: ~i" n^: 

: - -.."-. _:_:::_:. : ::_:.: _n . ._ ::; ns As r . is : l-.: '.-: : .L-Z.j 

suggests, it would be better, however, to restrict the term leuc- - 

iisis :■: :-Z::zzr :i_- unm -z :■: ^z.\ \ z — in : ^z-zz^::Z ~zr-. — hil-e 

^ .-. '-.-. in zzZzi zlzzzzZz.-z-z ~_; ii \z- - zZ^zz. :: - :::.- 

tmk, and a diminution in their number as kypoUxctmytosix. 

PiiTsi: !■:«:: HTTrrlru: : :~ -sis. ^:::::t:^:::_:::l 
leucocytes occurring in health is noted especially in children, during 
idie process of digestion, in pregnancy, following the use of cold 
"'::.:!-. -z . 

According to Hayem, about 18,000 leucocytes are found in the 
blood of infants during the first eighty hours of life, 8000 during 
TLr nrs: h zzzzzz.. ~zz.:.-. in :..:....::: i.^ri :::i_ --'■'-:■:.. ni:n:is zzz :: 
the fourth year 3000, and in adults and old age only 5000 are 
counted on an average, according to the same observer. 

An idea of the marked increase occurring during the process of 



THE BLOOD. 






digestion, constituting the physiologic "digestive leukocytosis " of 
Virchow, maybe formed from the accompanying diagram, to which 

two charts have been added, illustrating the diurnal variations iii 
the amount of haemoglobin and the number of red corpuscles (Fig. 
13). 



Fig. 13. 

Red corpuscles in 1 cbmm. of blood. 



ill. 








| 


A.M. 
10 


1 


2 






4 


( 


P.M. 

> 8 


10 


i 


_> 




> 


A.M. 
4 ( 


1 




I 






'.''' 














*> 














































5,4 
















\ 




























































\ 








^ 


U* 


V 


































o,0 


















v 




/ 






\ 


















































\ 


/ 


























































\ 


/ 
































































































1 





Hb. in 1 cbmm. of blood. 



Gms. 

0,140 



^rr~\ t^r^ 



0,135 
0,130 
0,1 



Leucocytes in 1 cbmm of blood. 























































































/ 


\ 


























































/ 




\ 
























































/ 


/ 


















1 


1 — 


— , 


S 




































/ 


























\ 


v 
















7.1 1 1 
















/ 






















/ 








S 






























/ 


' 




















/ 












\ 




























/ 




















\ 














\ 
















































\ 














\ 
























1/ 




































\ 


\ 






















1 






































\ 




/ 




























































/ 








o500 


















































\ 


/ 










.vim 


















































\ 


/ 









Showing the diurnal variations in the number of red corpuscles, the amount of haemoglobin, 
and the number of leucocytes. (Taken from Reinert.) 

This form of hyperleucocytosis appears to be more marked in 
health than in disease, and notably in gastro-intestinal diseases. 
Schneyer was thus able to note the absence of a digestive- hyper- 
leucocytosis in every one of his eighteen cases of carcinoma of the 
stomach, and records five similar eases described by Miiller. In 



GO CLINICAL DIA GNOSIS. 

almost all cases of ulcer of the stomach and of benign stenoses of 
the pylorus, on the other hand, the usual increase in the number of 
leucocytes could be established. Should further investigations 
confirm these results, it is apparent that an examination of the 
blood in this direction would be of the greatest importance in the 
differential diagnosis between carcinoma and ulcer of the stomach. 

A very marked increase is frequently noted after a cold bath, 
which, according to Thayer, may even amount to 284.6 per cent. 
In his own person on one occasion the leucocytes, which numbered 
3250 per cbmm. before the bath, rose to 12,500 twenty minutes 
later. As the observer reports, however, that he was blue and 
shivering at the end of his bath, the stimulus given can hardly be 
regarded as having produced only a physiologic effect. 

The physiologic hyperleucocytosis observed during pregnancy is 
particularly marked during the last five months, and appears to 
occur quite constantly in pri mi parse, while in multiparaa exceptions 
are frequently noted. In au analysis of thirty-one cases Eieder 
could thus note the existence of a hyperleucocytosis in twenty, the 
number of leucocytes varying between 10,000 and 16,000, with an 
average of 13,000 per cbmm. 

Pathologic Hyperleucocytosis. Under pathologic conditions 
an increase in the number of leucocytes is frequently observed and 
is a matter of great importance. 

A leukaemia, in which the greatest increase in the number of 
leucocytes is noted, may thus be diagnosed at once by an enumera- 
tion of the leucocytes, a single glance through the microscope often 
being sufficient to determine the diagnosis. This increase is most 
pronounced in cases of the lieno -myelogenous form, in which the 
proportion of white to red cells may be 1 : 10, 1 : 5, or even 1:1; 
and Osier states that cases have been recorded in which the leuco- 
cytes actually outnumbered the red corpuscles. In the lymphatic 
form of leukaemia the increase is not so marked, and the proportion 
of 1 : 10 but rarely exceeded. 

Aside from leukaemia a hyperleucocytosis is observed in all acute 
inflammatory diseases, and it may be said that the increase in the 
number of the leucocytes is directly proportionate to the degree of the 
local reaction, so that it is possible to predict in a given case whether 
or not a hyperleucocytosis will occur. In typhoid fever, for ex- 
ample, in which the local reaction is slight, no hyperleucocytosis, 
or one of only mild degree, will be observed, while with a compli- 



THE BLOOD. ( ; \ 

eating pneumonia or pleurisy, in which the local reaction is well pro- 
nounced, a correspondingly marked hyperleucocytosis will he found. 
This is most important, as complications iu this disease may thus 
often be discovered by an examination of the blood, and in conjunc- 
tion with the clinical symptoms a correct, or, at least, a probable, 
diagnosis may often be reached, which would have been out of the 
question otherwise. 

To cite only one example: A convalescent from typhoid fever 
suddenly complained of pains in the abdomen, particularly marked 
in the right iliac fossa, which increased within a few hours to such 
a degree that full doses of morphine and chloroform inhalations 
became imperative. Four hours later the patient was comatose, 
with a pulse ranging from 160 to 200 and a temperature of 105.5° F. 
At this stage an examination of the blood showed an approximately 
normal number of leucocytes. Within the next twenty-four hours 
icterus, accompanied by the passage of bile-colored urine and clay- 
colored feces, developed, and the next day a biliary calculus was 
found in the stool. The diagnosis of cholelithiasis was based upon 
the result of the blood-examination in conjunction with the clinical 
symptoms. 

An osteomyelitis may be similarly recognized at a time when the 
clinical symptoms in themselves alone would not warrant the diag- 
nosis. 

In pneumonia the degree of hyperleucocytosis may serve as a 
direct index of the amount of lung-tissue involved, disappearing 
during the crisis or even a few hours before it sets in. 

The hyperleucocytosis here is quite constant, excepting, according 
to Tschistovitch and v. Jaksch, certain cases in which it is absent, 
or but slightly marked, and which, according to the same authori- 
ties, are invariably fatal. The results reached at the Johns Hop- 
kins Hospital, however, do not appear to bear out the correctness 
of this view, as fatal cases were observed in which 45,000 and even 
114,000 leucocytes were counted per cbmm. Further investiga- 
tions in this direction are urgently needed, and, should the general 
results obtained by Tschistovitch and v. Jaksch be confirmed, a 
blood-examination in pneumonia would be of the greatest prog- 
nostic value. As in pneumonia, so also in erysipelas, the hyper- 
leucocytosis terminates by crisis. 

In phthisis hyperleucocytosis apparently only occurs when the 
disease has led to the formation of cavities. 



62 CLINICAL DIAGNOSIS. 

A cachectic hyperleucocytosis, often of great intensity, is noted in 
cases of malignant disease; but it is still an open question whether 
or not this is dependent upon the local reaction in the neighborhood 
of the growth. To judge from personal observations, the existence 
of a hyperleucocytosis in the differential diagnosis between malig- 
nant and benign diseases of the stomach invariably points to the 
former. 

General Differentiation of the Various Forms of Leuco- 
cytes. Upon ordinary microscopic examination three varieties of 
leucocytes can be distinguished. (Plate IT., Fig. 1, a.) Some are 
round, smaller than a red corpuscle, and provided with a large, 
round nucleus, which is surrounded by a very narrow rim of non- 
granular protoplasm. Others are met with which are likewise 
round, of the size of an ordinary red corpuscle, the large single 
nucleus being surrounded by a narrow zone of non-granular proto- 
plasm. The large cells, the bodies of which are filled with granular 
material, often hiding the nucleus from sight, are representatives of 
the third variety. 

Upon further examination differences may also be demonstrated 
in the character of the granulations. Some leucocytes will thus be 
observed in which these are very fine, giving the entire body of the 
cell a cloudy appearance, and usually obscuring the nucleus, which 
may be brought into view, however, together with its nucleoli, by 
treating the preparation with a drop or two of a 1 per cent, solution 
of acetic acid. On the other hand, very coarse granulations may be 
observed in certain leucocytes, while still others, as already pointed 
out, are apparently non-granular. 

Within late years Ehrlich has studied these various granulations 
in their behavior toward aniline-dyes, the results obtained being 
most interesting, and, as will be shown, of decided value from a 
clinical standpoint. He was able to demonstrate the existence of 
different chemical affinities between these minute particles of proto- 
plasm and the reagents employed. Some are thus only colored by 
acid stains, others again only by those of a basic nature, while still 
others are stained only by neutral stains. 

The Aniline-stains. Ehrlich divides the acid stains derived 
from coal-tar into two large groups: i. e., into stains which will 
color the granulations (see below) even when employed in concen- 
trated solutions of glycerine, and into those which can only be em- 
ployed in aqueous solutions. 



THE BLOOD. 63 

The first group contains : 

(1) The highly acid bodies belonging to the fluorescio series, viz., 
eosin, methyl-eosio, coocin, py rosin J and R; (2) the highly acid 
nitro-bodies, such as aurantia; (3) the two groups of sulpho-acids — 

i. <•., indulin, bengalin, and nigrosin, on the one hand, and the azo- 
stains, tropseolin, Bordeaux, and Ponceau, on the other. 

The second group contains: 

(1) Fluorescin and chrysolin; (2) ammonium picrate and naph- 
thvlamin-yellow; (3) orange and true yellow. 

Representatives of the basic stains are: fuchsin (rosanilin), the 
methyl derivatives of rosanilin, viz., methyl-violet, methyl-green, 
etc., the phenyl derivatives of rosanilin (triphenyl-rosanilin), roso- 
naphthylamiu, cyanin, safranin, etc. 

As an example of a neutral stain there may be mentioned the 
picrate of rosanilin. 

Differentiation of the Leucocytes according to their Be- 
havior toward Aniline-stains. According to their behavior toward 
these various pigments, Ehrlich has divided the granular leucocytes 
found in the blood into eosinophils, basophiles, and neutrophils. 
By the aid of his methods the following forms of leucocytes, the 
study of which is especially important in the differential diagnosis 
of leukaemia, may be made out in the blood. (Plate II., Fig. 2.) 

1. Small mononuclear leucocytes. These are mostly smaller than 
the red corpuscles or of equal size. They are devoid of granular 
matter, each cell being provided with a large, deeply-staining 
nucleus, surrounded by a narrow rim of non-granular protoplasm. 
As they appear to be formed, to a large extent at least, in the 
lymphatic glands, they are aiso spoken of as lymphogenic leucocytes 
or lymphocytes. 

The increase in the number of leucocytes observed in the lymphatic 
form of leukaemia occurs in this variety only, while the large mono- 
nuclear elements, as well as the polynuclear leucocytes, are at the 
same time relatively diminished to a considerable extent. In the 
lieno-myelogenous form, on the other hand, the lymphocytes are 
relatively diminished. A relative increase in the number of lympho- 
cytes is observed in healthy infants, in various diseases of infancy, 
in chlorosis, pernicious anaemia, secondary syphilis, in the late sta 
of typhoid fever, in certain cases of Basedow's disease, haemophilia, 
goitre, etc. 

2. Large mononuclear leucocytes. These are larger than the red 



64 CLINICAL DIAGNOSIS. 

corpuscles, their nuclei oval or elliptical in form, and surrounded 
with a somewhat wider zone of protoplasm, which, as in the first 
variety, is apparently non-granular. They probably represent a 
later stage in the development of the small mononuclear form. 
Some writers, however, still maintain that they are formed in the 
spleen and in the bone-marrow. They occur in increased numbers, 
in cases of chronic malaria, in measles, at the end of scarlet fever, 
etc. 

3. Cells which are of the same size as those belonging to the 
second variety, or a little smaller, and filled with very fine neutro- 
philic granules, the s-granulations of Ehrlich. The nucleus is a 
long body, which is twisted upon itself into irregular forms, often 
presenting a broken appearance, and conveying the impression as 
though several nuclei were present. Such leucocytes are hence 
spoken of as polynuclear neutrophilic leucocytes. As Ehrlich has 
suggested, the polynuclear appearance, however, is probably refer- 
able to post-mortem changes, the condition of the nuclei being in 
reality polymorphous. In accord with this view they have hence 
also been termed polymorphonuclear leucocytes. They also are sup- 
posed to represent a later stage in the development of the small and 
large mononuclear cells. While basophilic and eosinophilic granules 
have been found in all animals examined in this direction, it is in- 
teresting to note that neutrophilic granules occur only in man, an 
observation which may be of considerable importance in the medico- 
legal examination of the blood. The ordinary forms of hyperleuco- 
cytosis are referable to an increase in the number of these elements. 
All pus-corpuscles, moreover, according to Ehrlich, belong to this 
class. 

4. Cells are encountered in every specimen of blood, which appear 
to be transition forms between the second and third varieties. These 
are mononuclear, the nuclei, however, presenting a constricted ap- 
pearance, indicating that they are beginning to become polymor- 
phous. As a general rule, no granulations are found, but excep- 
tionally they do occur, when they are neutrophilic in character. 

5. Cells which are of the size of the third variety, provided with 
a polymorphous nucleus, and large, ovoid or roundish, highly refrac- 
tive, fat-like granulations, the ^-granulations of Ehrlich. These 
only take up acid stains, such as eosin, and the leucocytes are 
therefore spoken of as eosinophilic leucocytes. According to Ehrlich, 
they are derived from the bone-marrow only, and have hence also 



THE BLOOD. ,,;, 

been termed myelogenic leucocytes. There appears to be some doubt, 
however, as to the correctness of this view, as marked differences 
can be shown to exist between the eosinophilic leucocytes that are 
found in the circulating blood and those encountered in the bone- 
marrow. The latter are essentially myelocytes (see below), viz., 
mononuclear leucocytes, in which eosinophilic grannies are found. 
Their presence in the blood, according to recent researches, appears 
to be confined to leukaemia. Formerly an increase in the number 
of the ordinary eosinophilic leucocytes, which possibly represent 
the senile stage in the development of the small mononuclear 
variety, was regarded as almost pathognomonic of the lieno-myelo- 
genous form of leukemia. While an increase, both relative and 
absolute, in their number is observed in most cases of this disease, 
it does not occur invariably, and careful examinations have shown, 
moreover, that a similar increase may be noted in other diseases, 
and notably in true bronchial asthma, in certain diseases of the 
bones, the skin, the nervous system, in trichinosis, and at times 
even in health. In diminished numbers they are found during 
the process of digestion, in pneumonia, typhoid fever, diphtheria, 
influenza, after castration, etc. The phagocytes of the blood are 
essentially of this variety. 

6. Basophilic leucocytes are accidentally met with in the blood 
in various conditions, and especially in leukaemia, but are as yet of 
no diagnostic significance. The granulations, the y and o granula- 
tions of Ehrlich, appear to be the same as those observed in the 
so-called Mastzellen, found in connective tissue especially; the same 
term has hence been applied to this particular variety. 

Of late Xeusser has drawn attention to the fact that basophilic 
granules are not infrequently seen arranged about the nuclei of the 
mononuclear and polynuclear leucocytes, and he regards their pres- 
ence as characteristic of the so-called uric acid diathesis. As tuber- 
cular disease, moreover, is usually not seen in such cases, Neusser 
believes that their presence in cases of phthisis may be regarded as 
a favorable symptom. Futcher, on the other hand, was unable to 
confirm Xeusser' s results. Further researches, however, are neces- 
sary before definite conclusions can be reached. 

7. Still another form is found in the blood under pathologic con- 
ditions, notably in leukaemia, to which the term myelocytes ha- been 
applied, as they appear to originate only in the marrow of bone. 
These cells apparently represent an arrest or perverted form of 

5 



66 



CLINICAL DIAGNOSIS. 



development, being essentially large mononuclear leucocytes, the 
bodies of which are filled with neutrophilic granules. At times 
they acquire a very large size, exceeding that of all other elements 
occurring; in the blood, but never become amoeboid. 

The presence of large numbers of this variety, which is rarely 
seen in the blood under normal conditions and particularly when 
associated with an increased number of the ordinary leucocytes and 
the presence of so-called eosinophilic myelocytes, may be regarded 
as highly suggestive of the lieno-myelogeuous form of leukaemia, 
while they are usually absent in the lymphatic form. 

8. Certain polynuclear leucocytes may also be encountered in the 
blood under pathologic conditions, in which no granulations can 
be demonstrated with Ehrliclrs triple stain. Nothing is known of 
their significance. 

The leucocytes normally present in the blood occur in definite 
proportions, which are quite constant, as shown 
table: 

Polynuclear neutrophilic leucocytes 

Lymphocytes ....... 

Large mononuclear leucocytes and transition-forms 

Eosinophilic leucocytes ..... 

Mastzellen. less than 

The Drying- and Staining* of Blood. In order to obtain speci- 
mens of value cover-slips of the finest grade, carefully cleansed with 



in the following 



130-75 

20-30 
6 

2-4 
1.0 



per cent. 



Fre. 14. 




Ehrlich's cover-glass forceps. 
Fig. 15. 




Linsley's cover-glass forceps. 



absolute alcohol or with dilute nitric acid, are indispensable. Care 
should also be taken to handle the cover-glasses with forceps only, as 



THE BLOOD, 67 

the warmth of the fingers in itself is sufficient to cause post-mortem 
changes in the red corpuscles. For this purpose specially con- 
structed forceps, such as those suggested by Ehrlich, will be found 
of great assistance. (Figs. 14 and 15.) The tip of a finger, or 
preferably the lobe of the ear, should be cleansed with soap and 
water, alcohol and ether. A small drop of blood is theu received 
upon a cover-glass and spread out in such a manner that the layer 
shall not be thicker than the diameter of a red corpuscle. To this 
end it is most convenient to cover the drop of blood with a second 
cover-glass, pressure being avoided, and to draw the glasses apart 
in a horizontal direction. The same result may also be reached by 
spreadiug out the blood with the edge of a second cover-slip, a fine 
cameF s-hair brush, or a specially devised mica spatula. This step 
in the preparation of dried specimens is the most difficult, and 
requires a certain amount of experience as well as care. 

A number of specimens are thus prepared, and when dried at an 
ordinary temperature will keep almost indefinitely. 

If it is desired to make an early examination, the specimens are 
further fixed by exposure to a temperature of from 110°-115° C. 
for from 5-30 minutes. Immersion in absolute alcohol, or a 
mixture of equal parts of absolute alcohol and ether for half an 
hour, also answers the purpose. Very convenient is the use of 
formol, a mixture of 40 : per cent, formic aldehyde in methyl alco- 
hol and water. One part of formol is diluted with nine times its 
volume of water, and one part of the mixture thus obtained with 
nine times its volume of alcohol. The immersion of the specimen 
in this solution for but one minute is said to furnish admirable 
results. The continued exposure of the blood to a temperature of 
from 100°-120° C. for from one to two hours can thus usually be 
dispensed with, although it may be advantageously employed in 
special cases. For the purpose of fixing specimens by heat the 
use of a small coal-oil stove, upon which a copper plate measuring 
40 x 10 cm. is placed, will be found most convenient. Upon the 
plate the line corresponding to the desired temperature is ascertained 
by means of a series of drops of water extending from the middle 
toward either end, and noting the line at which bubbles will appear 
in the water. The specimens are then placed just inside of this 
line. When once properly regulated the apparatus, which may 
very advantageously be placed in a box so as to guard against 
currents of air, will be found to furnish a fairly constant tempera- 



6g CLINICAL DIAGNOSIS. 

ture. A drying-oven may. of course, be used for the same pur- 

j K 

When fixed according to one of the methods indicated, the dried 
specimeu is ready to be stained. For this purpose a number of 
solutions inav be employe the selection of the special mixture 

depending upon the particular points to be elicited. 

Staining with Eosin. A 0.1-0.5 per cent, aqueous solution 

or a 0.25-0.5 per cent, alcoholic solution is used, upon which the 
ad specimen is allowed to float for from ten to twenty minutes 
if the former is used, while oue-half or oue minute only is necessary 
in the case of the latter. It is then rinsed with water, dried between 
layers of rilter-paper, and mounted in xylol-balsam. 

The red corpuscles are stained a bright red. the protoplasm of the 
leucocytes faint red. while the eosinophilic granules are deeply 
colored. 

Staining with Ehelich'- Tei-glyceeixe Mixture. This is 
composed of 2 grammes each of eosin, aurantia. and nigrosiu in 30 
grammes of glycerine. The specimens are allowed to remain upon 
the stain for from sixteen to twenty-four hours, when they are 
rinsed in water, dried, and mounted as described. 

The red corpuscles are colored orange, the bodies of the leucocytes a 
dirty gray with dark nuclei, and the eosinophilic granules a bright red. 

Staivtxg with Eheli«:h"s H.emaT'oxylix-E'OSJx. The solu- 
tion is prepared by dissolxin_ 4-5 grammes of hematoxylin in a 
mixture of 100 grammes each of distilled water, alcohol, and gly- 

ine. To this solution 20 grammes of glacial acetic acid and an 
jss ;f alum are added. After exposure to the sim for four to 
six weeks about 1 per cent, of eosin is hnally added. The speci- 
men is left in the stain exposed to the sun in a covered beaker for 
twenty-four hours, when it is rinsed in water, dried, and mounted. 

The red corpuscles are colored a bright red. the nuclei of the 
normoblasts and megaloblaste a deep black, the bodies of the lei;. - 
cytes a light lilac, their nuclei a dark lilac, the eosinophilic granules 
a bright red. while the xlies : the lymphocytes are scarcely 
stained at all. and their nuclei appear onlv a shade lighter than 
those of the nucleated red i : as les. 

Staining with Ehrlich's rei-Acm Stain. This is the dif- 
ferential stain most ised at the Johns Hopkins Hospital, and one 
which usually furnisher lent results. It has the advantage 

also that an exposure of the specimen to the stain for six to eight 




THE BLOOD. 69 

minutes only is necessary. Its preparation requires some care, and 

it is important, furthermore, that the mixture should stand for one 
to two weeks before being used. Saturated aqueous solutions of 
aeid fuchsin, orange (J, and methyl-green are first prepared and 

allowed to stand until clear, when they are gradually mixed in the 
proportions indicated below: 



Fuchsin solution . 


9 c.c 


Distilled water 


6 " 


Orange solution 


18 " 


Methyl-green solution 


20 " 


Alcohol (94 per cent.) 


15 " 


Distilled water 


30 " 


Glycerine 


5 " 



After staining for from six to eight minutes the specimen is rinsed 
in water, dried, and mounted. 

The nuclei of the leucocytes are stained a greenish-blue, those 
of the red corpuscles nearly black, the red corpuscles orange, the 
eosinophilic granules red, and the neutrophilic granules a violet or 
a lilac color. (Plate II., Fig. 2.) 

Staining with Aronsohn and Philips' Modified Tri-acid 
Stain. Saturated aqueous solutions of orange G, acid rubin, and 
methyl-green are prepared, and the various ingredients mixed in 
the following proportions: 

Orange solution 

Acid rubin solution ...... 

Distilled water 

Alcohol ......... 

To this mixture are added : 

Methyl -green solution ...... 

Distilled water 

Alcohol 



55 


c.c. 


50 


n 


50 


i < 


65 


c.c. 


50 


(< 


12 


I < 



The mixture should stand for from one to two weeks before being 
used. 

A drop of the solution added to a Petri-dishful of water is 
employed for staining-purposes, an exposure of the specimen for 
twenty-four hours being required. The specimen is then rinsed off 
in water, absolute alcohol, cleared in origanum oil, and mounted. 

The various elements of the blood are colored as with Ehrlichia 
stain. 

Staining w^ith Chenzinsky-Plehn's Mixture. This con- 
sists of 40 grammes of a concentrated alcoholic solution of methylene- 



70 CLINICAL DIAGNOSIS. 

blue, 20 grammes of a 0.5 per cent, solution of eosin in 70 per cent, 
alcohol, and 40 grammes of distilled water. The specimen is stained 
for twenty-four hours. 

The red corpuscles assume the color of eosin, while the eosino- 
philic granules are bright red and the nuclei of the leucocytes blue. 

Staining with Ehrlich' s Nedtrax Mixture. This con- 
sists of five volumes of a saturated aqueous solution of acid fuehsin, 
to which one volume of a concentrated aqueous solution of methylene- 
blue is added slowly, while shaking. The mixture is treated with 
five volumes of distilled water and filtered after having stood for 
several days. The specimens are stained for from five to twenty 
minutes. 

The red corpuscles present the color of fuehsin, their nuclei as 
well as those of the leucocytes are black or a light lilac, the eosino- 
philic granules red, and the neutrophilic granules violet. 

Special Staining of Basophilic Leucocytes. The staiuing- 
fluid consists of 100 c.c. of distilled water, to which oO c.c. of a satu- 
rated alcoholic (absolute) solution of dahlia are added. Upon clear- 
ing, 10-12.5 c.c. of glacial acetic acid are added. The specimen is 
stained for from five to ten minutes. A saturated aqueous solution 
of methylene-blue may be employed for the same purpose and in 
the same manner. 

With the exception of bacteria, only the basophilic leucocytes are 
stained (red), while pus-corpuscles are but faintly tinged. 

In order to stain the perinuclear basophilic granules of Neusser 

the following modified mixture of Ehrlich should be employed : 

Saturated aqueous solution of acid fuehsin 
Saturated aqueous solution of orange G. 
Saturated aqueous solution of methyl-green . 
Distilled water ..... 
Absolute alcohol ..... 
G-lycerine 

A differential enumeration of the various forms of leucocytes can 
only be carried out in stained specimens, Ehrlich' s tri-acid stain 
being the most useful for this purpose. From 1000-1200 leuco- 
cytes at least should be counted in order to obtain reliable results. 
The use of Zeiss' s net-micrometer will be found of great value. 

As will be described, moreover, the actual number of leucocytes 
contained in one cbmm. of blood may be readily ascertained in an 
indirect manner by counting the number of leucocytes and red 
corpuscles in stained specimens (see page 75). 





50 


:.e. 




70 


if 




SO 


u 




150 


" 




80 






20 





THE BLOOD. 



71 



The Plaques. 

In addition to the Leucocytes and erythrocytes large numbe 
small, roundish elements are encountered in the blood, which are 
free from coloring-matter and may be frequently observed collected 
into small heaps, resembling bunches of grapes. These are the 
blood-plates or plaques of Bizzozero. According to Hayem, they 
represent ordinary red corpuscles in an early stage of development, 
and have hence been termed hecmatob lasts. This opinion, however, 
is not shared by many hnematologists. 

According to Osier, they number from 200,000 to 500,000 per 
cbram. under normal conditions, and are said by Hayem to occur 
in greatly diminished numbers in the blood in pernicious anaemia. 
This observation, however, lacks confirmation. In order to demon- 
strate their presence the drop of blood should at once be mixed with 
Hayem' s fluid (see p. 72). 

The Enumeration of the Corpuscles of the Blood by the 
Method of Thoma-Zeiss. 

Of the various instruments employed for the enumeration of 
blood-corpuscles, that of Thoma-Zeiss appears to be the most satis- 
factory. (Fig. 16.) 

Fig. 16. 







0.100 mm. 
¥W mm. 







\d 1 

I o 

%. J 











Thoma-Zeiss blood-counting apparatus. 



It consists of a capillary pipette (S) having a bulb in its upper 
third, the lower end being graduated in parts numbered from 0.1 
to 1, while above the bulb a mark bearing the number 101 is 



72 CLINICAL DIAGNOSIS. 

placed. With this goes a counting-chamber (B) measuring exactly 
0.1 mm. in depth, the floor of which is ruled into sets of 16 small 
squares, each small square underlying a space of T qVo cbmm. 

Enumeration of the Red Corpuscles. In order to count the 
red corpuscles with this instrument the tip of a finger, or, better 
still, the lobe of the ear, is punctured with a sharp-pointed scalpel, 
after having been carefully cleansed with soap and water, alcohol, 
and finally with ether. The exuding blood is drawn into the capil- 
lary tube to a given mark, generally to 1 or 0.5, according to the 
degree of dilution desired, care being taken that no pressure is 
exerted upon the finger and that the tip of the instrument comes 
in contact with the blood only. The point of the tube is then 
rapidly and carefully wiped, and the blood diluted, as a rule, with 
a 3 per cent, solution of common salt, which is drawn into the 
pipette until the 101 mark is reached. 

Toison's fluid is still more convenient as a diluent, as the leuco- 
cytes are stained by the methyl-violet, and thus rendered more 
easily visible. Its composition is the following : 



Distilled water . 
Glycerine . 
Sodium sulphate 
Sodium chloride 
Methyl-violet 



160 parts. 
30 " 
8 " 
1 part. 
0.025 part. 



Other solutions, such as a 15-20 per cent, solution of magnesium 
sulphate, a 5 per cent, solution of sodium sulphate, Hayern's or 
Pacini's fluid, may also be employed for the same purpose. 

Formula of Hayem's fluid: 

Bichloride of mercury 0.5 grm. 

Sodium sulphate 5.0 grms. 

Sodium chloride 2.0 " 

Distilled water 200.0 " 

Formula of Pacini's fluid: 

Bichloride of mercury 2.0 grms. 

Sodium chloride . . . . . . 4.0 " 

Glycerine . . . . . . . . 26.0 " 

Distilled water 226.0 " 

The contents of the bulb are now thoroughly mixed by shaking, 
in which the glass bead (E) contained in the bulb aids very mate- 
rially. The contents of the capillary tube are then cautiously 
expelled, as this practically contains only the diluting-fluid; a 



THE BLOOD. ;;> 

drop of the mixture is placed in the counting-chamber, and the 
cover-slip (r) adjusted, bubbles of air being carefully excluded. 
When properly prepared, Newton's colored rings should be seen 

at the margin of the drop. After allowing the corpuscles to settle 
— from three to five minutes are generally sufficient — they are 
counted. At least one whole field, or, if special accuracy be re- 
quired, two whole fields, should be gone over — i. e., 200 or 400 
small squares, respectively, wheu counting the red, aud at least 
four whole fields wheu counting the white. 

It is convenient to count the red corpuscles in sets of four small 
squares, lying side by side in a horizontal direction, note being 
taken of every corpuscle that touches the boundary-lines of the 
large squares, no matter whether the body of the cell lies inside or 
outside of these lines. It will be noted that every large square is 
separated from its neighbor, both horizontally aud vertically, by a 
row of small squares traversed by a mesially placed line, which 
serves as a guide to the next large square. (Fig. 17.) As a gen- 
eral rule, it will be found most convenient to ignore these interme- 
diary squares, account being taken only of the large ones. 











Fig 


17. 










\°. 


»%• 


*' * 




o '« 


:}i 


\ 


• 


Jet 




/ 


.« 


,v, 




i °s 


• 5 c 




', 




. «c 


,- 




..•l 










»»'o 


* 


• 


:• 


.v. 




° 


;•; 




* 


<■ r 


»'o ° 


/; 


■; 


° °o 


• : 






, 


'« 


„ ,' 


v° 


; 


• 


3 ° » 




V 


. v 


; 


" 


%v 


.v: 


: 


.: 


' c°° 


v° 


*•/ 


.°v. 


{ 


• 




•o C 


J? 




- »,* 


.* ■ 


'- ° 


,•„* 








-. \ 








o .? o 


. *o 


: r" 


•V. 


& 


■\- 


":} 


':• 


I> 


$ 


{v 



Appearance of blood in the Thoma-Zeiss cell. 



In order to calculate the number of red corpuscles contained in 
one cbmm. of blood the total number noted is divided by the 
number of small squares counted, the result giving the average 
number contained in one small square — i. e., in -fa-^ cbmm. One 
cbmm. of the diluted blood will then contain 4000 times this num- 
ber, and one cbmm. of undiluted blood the product of this figure 
and the degree of the dilution. 

Example: Supposing that 1200 red corpuscles were counted in 
400 small squares, the average number contained iu one — /. e., in 



74 CLINICAL DIAGNOSIS. 

:nnnF cbmm. of diluted blood — would be 3, corresponding to 12,000 
corpuscles for each cbmm.; supposing, further, that the blood was 
diluted 200 times, there would be 2,400,000 in one cbmm. of the 
undiluted blood. ' 

Enumeration of the "White Corpuscles. With this instru- 
ment the leucocytes, when present in increased numbers, may also 
be counted, at least four whole fields, as indicated above, being 
taken into account. 

With an approximately normal number of leucocytes, however, 
it is necessary to resort to special pipettes, which are constructed so 
as to permit of obtaining a mixture of 1 : 10 or 1 : 20. With the 
diluting-fluids mentioned above it would be impossible, however, to 
count the leucocytes in a mixture of this proportion, as a large num- 
ber would be concealed by the red corpuscles. A 0.3-0.5 per cent, 
solution of acetic acid is therefore used, which destroys the red cor- 
puscles and renders the nuclei of the white more distinct. In the 
absence of a special instrument, an ordinary 1 cbmm. pipette accu- 
rately graduated in tenths may be employed. 0.9 c.c. of the acetic 
acid solution is placed in a watch-crystal and there mixed with 0.1 
c.c. of blood, when the counting-chamber is filled and covered as 
described. In order to obtain greater accuracy the entire field of the 
microscope is now counted, a lower power being employed with 
which the rulings are just visible. The cubic contents of the field 
are now determined according to the formula Q = rrr 2 X 0.1. 
Q represents the cubic contents to be determined; r, the radius, 
which is readily ascertained by noting the number of vertical lines 
which cross the field, bearing in mind that the distance between 
two of these is equivalent to -^ mm. (the area of each small square 
being -^-^ mm.), and dividing the transverse distance by 2; the 
value, ~, is constant, 3.1416; 0.1 represents the depth of the 
chamber. 

If n represents the number of white corpuscles contained in the 
field, the cubic contents of which are Q, the number of corpuscles, 
N, contained in one cbmm. of the diluted blood is ascertained accord- 
ing to the equation: 

Q : ii : : 1 : N and N = -. 

Q 
As the blood has been diluted ten times, the value of lST for the 
non-diluted blood will be f£, where n represents the total number 
of leucocytes and f the number of fields counted. 



THE BLOOD. 75 

Example : Supposing the number of leucocytes found in 50 fields 
to have been 600, and the cubic contents of each field 0.03925 
cbmm., the total number of leucocytes contained in one cbnnu. of 
undiluted blood, according to the equation : 

N = Hln = 10X600 wouldbe305 7. 
f.Q 50X0.03925 

Special care should be taken to keep the pipette in clean con- 
dition. After use it should be rinsed with (1) the diluting-fluid, 
(2) distilled water, (3) absolute alcohol, and (4) ether. If dust or 
coagulated blood adhere to the pipette, it should be removed by 
repeated rinsings with strong acids or alkalies, assisted if necessary 
by a bristle. 

Indirect Enumeration of the Leucocytes. 

The number of leucocytes may also be ascertained in an indirect 
manner by accurately counting the number of red corpuscles and 
leucocytes in dried and stained specimens with a Zeiss net-microm- 
eter, the ratio between the two varieties being thus ascertained. 
AVith the Thoma-Zeiss apparatus the number of red corpuscles 
contained in one cbmm. of blood is then determined, when the 
corresponding number of leucocytes is found according to the 
equation : 

1 : r : : L : R, and L = 1R = 7142, 
r 

where 1 and r represent the number of leucocytes aud erythrocytes, 
respectively, counted in the dried specimens, and where L indicates 
the unknown number of leucocytes and R the number of red cor- 
puscles contained in one cbmm. of blood, as determined with the 
Thoma-Zeiss instrument. 

Example: Supposing that 700 red corpuscles and only one leuco- 
cyte were counted in the dried specimen, and that an estimation of 
the erythrocytes with the Zeiss apparatus indicated the presence of 
5,000,000 in one cbmm. of blood, the corresponding number of 
leucocytes would be 71 12, as is apparent from the calculation : 

L = 1R = 1 - 5000000 — 7142 
r 700 

Notwithstanding the apparent simplicity of the process of blood- 
counting, considerable experience is required in order to obtain 



76 



CLINICAL DIAGNOSIS. 



results that are free from unavoidable errors. In using the Thoma- 
Zeiss apparatus errors of more thau 2-3 per cent, should not occur. 

The Hsematokrit. 

Within late years the centrifugal machine has also been applied 
to blood-counting, and it may be safely asserted that should the 

Fig. 18. 




Fig. 19. 




Daland's hseuiatokrit. 



THE Ul.ooi). 



77 



claims set forth for the bsematokrit, a- the instrument is termed, 
be borne oat by actual experience, the use of cytometers, which is 
both tedious and fatiguing, will soon be abandoned. 

Daland's latest modification of this instrument, originally devised 

by Sedin, is represented in the accompanying illustrations (Figs. 
IS, lit, '20, 21), and can be strongly recommended to both hospital 

FlG. 20. 




Fig. 21. 




Duliind's hii-matokrit. 



phvsieians and those engaged in general practice. It consists essen- 
tially of a metallic frame (Fig. 1!)), supported upon a spindle which 
can be rotated at high speed, one single revolution of the large 



78 CLINICAL DIAGNOSIS. 

handle causing 134 revolutions of the frame. Two glass tubes 
50 mm. in length and having a diameter of 0.5 mm. accompany 
the instrument. Each tube (Fig. 21) bears a scale ranging from 
to 100, the individual divisions of which are rendered easily 
visible by a lens-front. The outer ends of the tube fit into small, 
cup-like depressions, the bottoms of which are covered with thin 
rubber. The inner extremities are held in position by springs. 
The instrument should be firmly secured to a solid table and oiled 
daily when in use. 

To examine the blood, a rubber tube, provided with a mouth- 
piece (Fig. 22), is slipped over the end of one of the glass tubes, 
when the latter is filled completely by suction from a drop of blood 
obtained from the finger or the ear. The blunt point of the tube 

Fig. 22. 




Suction-tube of Daland's hsematokrit. 

is then quickly covered with the finger and the tube fixed in the 
frame. This is rotated at a speed of 10,000 revolutions for two 
or three minutes, when the volume of red corpuscles is directly 
read off. In healthy individuals the volume of red corpuscles is 
about 50 per cent., so that in a given case a proportionate expres- 
sion of the percentage of corpuscles, as compared with the normal, 
can be obtained by multiplying the figure upon the scale by two. 

As it has been ascertained that 1 per cent, by volume represents 
about 100,000 red corpuscles, it is only necessary to add five ciphers 
to the percentage- volume found in order to obtain the number of 
red corpuscles in one cbmm. of blood. 

Example: Supposing that in a given case the reading was 35; 
by multiplying this figure by 100,000, 3,500,000 would represent 
the number of red corpuscles contained in one cbmm. of blood. 

The amount of haemoglobin contained in each corpuscle is ascer- 
tained approximately by dividing the amount of haemoglobin deter- 
mined by means of Fleischl's instrument by the number of cor- 
puscles found with the haematokrit. 

If normal blood be examined with the haematokrit, the leucocytes 



THE BLOOD. 79 

will be seeo to form a narrow white hand at the central end of the 
column of red corpuscles. If a hyperleucocytosis exist, it is readily 



BACTERIOLOGY AND PARASITOLOGY OF THE BLOOD. 

It is generally admitted that micro-organisms do not normally 
ovenv in the blood; in conditions which may be said to stand mid- 
way between health and disease, however, they are at times met 
with. In patients suffering from furuncles, for example, bacteria 
may be found in the skin, in the lymphatic glands, and even in the 
blood of neighboring tissues, other symptoms of disease being ab- 
sent. To this condition the term u latent microbism" has been 
applied by Verneuil. 

Under truly pathologic conditions, on the other hand, micro- 
organisms are not infrequently found, and an examination with 
this view will often lead to a correct diagnosis. 

Physicians who, in our latitudes at least, do not resort to the 
microscope in fever cases, certainly ignore a most important aid to 
diagnosis. 

For ease of reference the various organisms that are met with in 
the blood in disease will be described under the headings of the 
respective diseases in which they are found. 

Typhoid Fever. 

In typhoid fever Eberth's bacillus (Plate VIII., Fig. 3) may 
at times, though rarely, be demonstrated in the blood, particularly, 
it is claimed, when taken from the roseolar spots. As an aid to 
diagnosis, however, no reliance should be placed upon the results 
of such an examination. 

WidaVs Serum-test. 

Very much more important is the fact that the blood-serum of 
patients afflicted with typhoid fever possesses the property of caus- 
ing arrest of motility and the agglutination of the specific bacilli. 
This observation, originally made by Pfeiffer, was first utilized for 
diagnostic purposes by Widal. The method which bears his name 
has now been quite generally adopted in the clinical laboratory, and 
must be regarded as a most valuable aid in the diagnosis of typhoid 



80 CLINICAL DIAGNOSIS. 

fever. Whether or not the serum-test is of greater value than the 
diazo-reaction of Ehrlich still remains to be seen. Like this, it is 
open to several objections. The principal ones are the following : 
1. It may be altogether absent in true cases of typhoid fever. 
This, however, is rarely the case. 2. The reaction may not be 
obtained before the end of the third week or may even be delayed 
until a relapse occurs, as the writer was able to observe in a recent 
case. 3. A positive result may be reached even after months and 
years following an attack of typhoid fever. 4. There are cases in 
which immunity against the disease apparently exists and in which 
distinct agglutination and loss of motility are observed in healthy 
individuals who have never passed through any serious illness. 
5. The reaction has also been observed in various other diseases, 
such as acute miliary tuberculosis, tubercular peritonitis, phthisis, 
heart-disease, etc. The number of such cases, however, which have 
thus far been reported is very small, and it is quite likely that 
future investigations will show that the positive results obtained 
are referable to some error of technique, as the method has scarcely 
reached its highest degree of perfection. The majority of observers 
are quite unanimous in affirming that the reaction is only observed 
in connection with typhoid fever. Only a positive result, however, 
is of value. 

Three methods of examination are available, of which the first is 
probably the most reliable. 

1. After careful disinfection of the arm 5 or 6 c.c. of blood are 
withdrawn from one of the superficial veins by means of a steril- 
ized hypodermic syringe and placed in a sterilized test-tube meas- 
uring from 10 to 12 cm. in length. The blood is allowed to stand 
until the serum has separated from the clot, which may be hastened 
by loosening the coagulum from the walls of the tube with a plati- 
num needle. Eight drops of the serum are added to 4 c.c. of nutrient 
bouillon, which should be as nearly neutral as possible, when the 
mixture is inoculated with one oese (platinum loopful) of a fresh 
bouillon-culture of the typhoid bacillus, not more than twenty-four 
hours old. The tube is kept at a temperature of 37° C. for twenty- 
four hours. At the end of this time and frequently earlier already 
the bouillon will be absolutely clear, or very nearly so, while little 
flakes, composed of the bacilli, will be seen at the bottom and ad- 
hering to the sides of the tube, if the case under observation is one of 
typhoid fever; otherwise the bouillon has become uniformly cloudy, 



THE BLOOD. ,Sl 

and a true sediment does not occur. A pseudo-reaction may also 
occur at times, which should not be confounded with the one just 
described. Innumerable macroscopic, dust-like particles will then 
be seen scattered throughout the fluid, which can be readily distin- 
guished from the cloudy appearance of non-typhoidal specimens. 
It has been suggested that this result is obtained in cases of intense 
infection with the bacillus coli communis. Should any doubt arise 
it is only necessary to keep such tubes for a few hours longer at a 
temperature of 37° C, when it will be noticed that the dust-like 
aspect has given place to the ordinary cloudy appearance observed 
in cases which are not typhoid fever. 

2. A small amount of blood, obtained by puncturing the ear, is 
received in a suitable receptacle, which can be sterilized in a spirit 
flame. A drop of the serum is mixed with 25 drops of a fresh 
bouillon-culture (sixteen to twenty-four hours old), and one drop of 
the mixture directly examined upon a cupped slide with a ^ oil- 
immersion lens. If the case in question be one of typhoid fever, 
rather large conglomerations of agglutinated, motionless bacilli will 
then be found evenly scattered throughout the field of vision, while 
the interspaces are either entirely free from bacilli or very nearly 
so. If necessary, the observation should be continued for two hours; 
but, as a rule, a positive result is already obtained within thirty min- 
utes if the case be one of typhoid fever. 

3. Two or three drops of blood are received upon a slide or a 
piece of paper and allowed to dry, care being taken that the speci- 
men is not exposed to dust. A drop of distilled water is then 
placed upon the blood and allowed to remain for several minutes, 
when it is washed off with five or ten drops of the bouillon-culture 
and examined as just described. It is interesting to note that the 
dried blood retains its agglutinative properties for weeks and even 
months. 

This method is, of course, the simplest for the general practi- 
tioner, and is the one generally employed in municipal bacteriologic 
laboratories. The results, however, are less reliable than those 
obtained with the second, and particularly with the first. 

Pneumonia. 

Recent researches have brought to light the interesting fact that 
in fatal cases of acute croupous pneumonia the specific diplococcus 

6 



82 CLINICAL DIAGNOSIS. 

is quite commonly present in the blood, while in cases ending in 
recovery it is only exceptionally encountered. The writer found, 
as a matter of fact, that a positive result is obtained in more than 
89 per cent, of the fatal cases. The invasion of the blood usually 
occurs twenty-four to forty-eight hours ante mortem, but may also 
take place at an earlier date or be delayed. From the standpoint 
of prognosis a bacteriologic examination of the blood may thus be 
of considerable importance. It should be remembered, however, 
that while a positive result is always a symptom mali ominis, there 
are cases on record in which recovery occurred notwithstanding the 
presence of diplococci in the blood. In such cases a metastatic in- 
fection has probably occurred. 

The examination, which should be repeated every day, is con- 
ducted as follows : After disinfection of the arm one of the super- 
ficial veins is compressed with a finger and punctured with an 
ordinary hypodermic syringe, which has been previously sterilized 
in boiling water. Five c.c. of blood are aspirated and agar-tubes 
— liquefied at 40° C. — inoculated, each with 1 c.c. of the blood. 
Plates are then prepared and kept at a temperature of from 35°- 
37° C The colonies number from 2 to 200, and appear as small, 
round, grayish, jelly-like drops, which are quite characteristic. 
During their growth they cause a greenish discoloration of the 
blood-agar. Other bacteria possess the same property, but in a 
less marked degree than the diplococcus pneumoniae. 

The individual organism (Plate IX., Fig. 2) is capsulated and 
usually occurs in pairs, arranged end-to-end or in short chains. 
At times, however, the chains are quite long, and it may then be 
difficult to distinguish it from certain streptococci. It is easily 
stained with the usual aniline-dyes. In order to differentiate the 
capsule the following method, suggested by Welch, is best em- 
ployed : Spread and dried cover-glass preparations are treated first 
with glacial acetic acid, which is allowed to drain off, and is replaced 
(without washing in water) with aniline gentian-violet solution. 
The stainiug-solution is repeatedly added until all the acid is 
displaced. The specimen is now washed in a weak salt-solution 
(about 2 per cent.), and examined in this, and not in balsam. The 
capsule and coccus can then be differentiated. 

The organism also grows on gelatin without causing its liquefac- 
tion. 



THE BLOOD. 



83 



Sepsis. 

The importance of a careful bacteriologic examination of the 
Wood in cases of septic infection has now been definitely established. 
Large quantities of blood are, however, necessary, and reliance 
should never be placed upon a microscopic examination of a single 
drop. In doubtful cases it is best to cup the patient and to inocu- 
late agar-plates and bouillon-tubes with the serum. The animal 
experiment, viz., the injection of 0.5 to 2.0 c.c. into the peritoneal 
cavity of white mice will also be found most valuable. Petruschky 
has shown that in severe cases of septic infection it is almost always 
possible to find streptococci in the blood, while in the milder cases 
a negative result is reached. He has found, moreover, that while 
as a general rule the presence of streptococci will justify a grave 
prognosis quoad vitam, death does not necessarily occur in every 
case. His results are tabulated below: 



Negative Results. 

Deaths. 
5 cases of puerperal fever 1 

2 " phlegmonous abscess associated with erysipelas . 

3 " simple erysipelas ....... 

8 u erysipelas (convalescing) . . . . .0 

1 " endocarditis 

1 " pleurisy with effusion 

1 " " with pericarditis . . . . .0 

2 " pneumonia 1 

2 " acute articular rheumatism 

1 " scarlatina ........ 

5 " typhoid fever ....... 

7 " phthisis (in 3 of which a general pyogenic infection 

was found post mortem ; 2 streptococci) . . 4 



Positive Results. 

5 cases of sepsis following phlegmonous abscesses 
or pulmonic infection (4 streptococci, 
1 staphylococci) ..... 

9 " puerperal infection (8 streptococci, 1 
staphylococci) ..... 

1 case of ulcerative endocarditis (streptococci) 

2 cases of mixed infection (streptococci) 



Deaths. Recoveries. 



Streptococci are frequently met with in the blood after death from 
diphtheria, while the staphylococcus aureus and Loeffler's bacillus 



84 CLINICAL DIAGNOSIS. 

are more rarely seen. In scarlatinal sepsis streptococci have like- 
wise been found. 

Of the other micro-organisms which may be met with in septic 
conditions the diplococcus pneumoniae is the most common. It has 
been found in peritonitis, associated with carcinoma of the uterus, 
in cases of suppurative oophoritis, following childbirth, and in cases 
of biliary abscess at the time of the chill. Friedlander's bacillus 
was also found in the latter disease. In a case of gonorrheal sep- 
ticaemia reported by Thayer and Blumer the gonococcus was found 
in the blood during life. Proteus vulgaris has been found in a few 
instances. 

Staphylococcus pyogenes aureus occurs in the form of minute 
spherical bodies, averaging about 0.8 fi in diameter, which readily 
stain with the basic aniline-dyes, as also with Gram's method. They 
usually occur in clumps, but may also be seen in pairs and in short 
chains. The organism grows on all culture-media, and in the pres- 
ence of oxygen gives rise to the formation of an orange-yellow 
pigment. Gelatin is rapidly liquefied; it coagulates milk and 
clouds bouillon. The staphylococcus pyogenes albus and citreus 
differ from the aureus by the absence of pigment in the first and by 
the formation of a lemon-yellow pigment in the second. 

Streptococcus pyogenes (Plate III., Fig. 1) occurs in chains of 
spherical cocci which usually vary from four to twenty in number. 
The size of the individual organism is somewhat greater than that 
of the staphylococcus, but may vary even in one and the same chain. 
It is readily stained with the basic aniline-dyes and also with 
Gram's method. It grows on all culture-media at the temperature 
of the room, forming small gray, granular colonies on agar and 
gelatin. As a rule, it does not liquefy gelatin, and it may or may 
not coagulate milk and cloud bouillon. Several varieties are recog- 
nized, viz., streptococcus brevis, which forms short chains; strepto- 
coccus longus, which occurs in long chains; streptococci which 
render bouillon cloudy, and those which do not; streptococci which 
form flocculent or sandy or scaly or viscous sediments. 

The streptococcus conglomeratus grows without clouding the bouil- 
lon, in the form of dense, separate particles, scales, or thin membranes 
at the bottom and sides of the tube, and on shaking the sediment it 
breaks up into little specks, without producing uniform, diffuse 
cloudiness. The chains are long and interwoven in conglomerate 
masses. (Welch.) 



PLATE III 



no. 






, I 






N '• 



1 « ) 



Streptococcus Pyogenes. (Abbott 



ric 2. 




A 



Bacillus Anthracis, highly mag- 
nified to show Swellings and Con- 
cavities at Extremities of the Single 
Cells. 



FIG. 3 



Qo 







o 



\ - ,rO 



P 0° /{ 



/ :i 



c&%9 



O 



Spirilla of Relapsing Fever. 
(v. Jakseh.) 



FIG. 4. 



y 



*3 "* ^ 




# 














SS 





m 









& 







<U*\ 



t&u 



■A§> 



L. 6CHMIDT, FEC. 



Malarial Blood Stained with Chenzin^ky-Plehn's Solution. (Personal Observation.) 



THE BLOOD. 85 

Anthrax. 

The bacillus of anthrax, as tirst pointed out by Pollender, Brouell, 
and Davaine, is frequently met with in the blood, where it should 
be sought for in doubtful cases by staining according to Loeffler's 
method. To this end cover-glass preparations are floated for five 
to ten minutes upon a mixture of 30 c.c. of a concentrated alcoholic 
solution of methvlene-blue and 100 c.c. of a 1 : 10,000 solution of 
potassium hydrate; they are then washed for five to ten seconds in 
a 0.5 per cent, solution of acetic acid, treated with alcohol, dried, 
and mounted in balsam. Thus stained, the bacilli appear as rods 
measuring from 5 a. to 12 n in length by 1 u in breadth, usually 
presenting a segmented appearance, the extremities being slightly 
thickened. Spores are not found, as the organism multiplies by 
fission. When present in large numbers it is not even necessary 
to stain, as the organisms can then be seen without difficulty in 
fresh specimens. (Plate III., Fig. 2.) 

In doubtful cases in which a microscopic examination of the blood 
yields negative results a few c.c. of the blood may be injected into 
a mouse or a guinea-pig, in the blood of which the bacilli will soon 
be found in enormous numbers if the disease be anthrax. 

Acute Miliary Tuberculosis. 

In acute miliary tuberculosis tubercle-bacilli have repeatedly been 
observed in the blood, but while their presence may be regarded as 
pathognomonic of the disease, the search for them is most tedious 
and often in vain. Nevertheless a careful examination of the blood 
is indicated in doubtful cases, but the fact should ever be borne in 
mind that only a positive result is of value. 

For methods of staining and a description of the tubercle-bacillus 
the reader is referred to the chapter on Sputum. 

Glanders. 

In glanders the specific bacillus is constantly present in the blood, 
and may be demonstrated by staining the dried preparations on a 
cover-glass for five minutes with a concentrated alcoholic solution 
of methylene-blue, mixed just before using with its own volume of 
a 1 : 10,000 solution of potassium hydrate. From this mixture the 



g(j CLINICAL DIAGNOSIS. 

specimen is pa- I for 2 second * two into a 1 per cent, solution of 

acetic acid which has been tinged a faint yellow by the addition 
of a little tropa?olin 00 solution: it is then decolorized by washing 
in water containing two drops of concentrated sulphuric acid and 
..ne drop of a 5 per cent, solution of oxalic acid for every 10 c.c. 

Fig. 23. 



gjr& 


' S 


" 


/€. 


<z 


<k 




/$m 






'' /- 



BaciUus of glanders. (Abbott.) 

In specimens thus stained the bacilli appear as short rods, meas- 
uring 2 //. to 3 /.'. in length 1 )-4 ft in breadth, often con- 
taining a spore at one end. (fig. 23/ 

Influenza. 

In influenza a specific organism has been described by Pfeiffer and 
Kitasato as occurring in the sputum: it is also constantly present in 
the blood of such patients. The organism in question appears in 
the form of minute rods measuring 0.1 u. in breadth by 0.5 v. in 
length, occurring either singly or in chains of threes or fours. In 
suitably prepared specimens, owing to the fact that their poles take 
up the stain more readily than the middle portion, they convey the 
impression of diplococci. 

Canon advises the following met « demonstrating their 

presence in the blood : Cover-glass preparations that have been 

allowed to dry at an ordinary : :ure are placed in absolute 

alcohol for five minutes and then stained at a temperature of 37 : C. 

for from three to six hours with Chenzinsky-Plehn's solution 'see 

. The specimen- are then washed in water, dried between 

- of filter-paper, and mounted in balsam. Stained in this 

manner the red corpuscles are colored red, and the leucocytes, as 

well as the bacilli, blue. As a rule, only from four to twentv of 

these are found in one preparation, usually occurring singly, but 

9. Owing to the fact that thev are found in the 



THE BLOOD. #7 

blood only during the acme of the disease, ("anon recommends the 
examination of the sputum for diagnostic purposes, a view will) 
which personal observations are entirely in accord. 

Relapsing Fever. 

Relapsing fever is characterized by the presence in the blood, and 
here only, of spirilla or spirochsetae which bear the name of their 
discoverer, Obermeier. In order to search for these organisms no 
special precautions are necessary. After having carefully cleansed 
the finger as described, a drop of blood is mounted upon a very thin 
cover-glass. This is directly inverted upon the slide, when the 
specimen is ready for examination; an oil-immersion lens is not 
required. Attention is drawn to the presence of these organisms 
by certain disturbances noticeable among the red corpuscles, and 
upon careful examination it will be seen that these are caused by 
the wriggling movements of the spirilla. The spirochete Ober- 
meieri are long, slender filaments, measuring from 36 p to 40 /j. in 
length by 0.3 a to 0.5 fi in breadth, and present from eight to 
twelve incurvations of equal size with tapering extremities. (Plate 
III., Fig. 3.) These last two characteristics serve to distinguish 
this species from that described by Ehrenberg, in which the radius 
of the incurvations is not the same in all, and in which the extremi- 
ties do not taper. 

The number of spirilla that may be found in a drop of blood 
varies, being greater during the access of the fever, when twenty, 
or even more, may be observed in the field of the microscope. They 
occur either singly or in bunches of from four to twenty, specimens 
sucli as those figured in the table being frequently seen. In the 
quiescent stage they are sometimes arranged in the form of rings or 
of the figure 8. After the crisis they seem to disappear entirely, 
and their presence during an afebrile period may therefore always 
be regarded as indicating a pseudocrisis. During the afebrile 
periods small, bright, round bodies have been described as occur- 
ring in the blood, which according to some are spores, but according 
to others merely represent debris of the spirilla. 

Culture-experiments have not been very satisfactory, although 
Koch, at a temperature of from 10° to 11° C, observed an increase 
in their number. 

That confusion should ever arise in distinguishing the spirilla of 



88 CLINICAL DIAGNOSIS. 

relapsing fever from the free flagella observed at times in malarial 
fever appears very improbable to the writer. 

Malaria. 

The discovery of a specific micro-organism belonging to the class 
of protozoa, the plasmodium malar ice of Laveran, in the blood of 
malarial patients, and of its invariable presence in the different 
forms of this disease, must be regarded as one of the most impor- 
tant in clinical medicine. This is not the place to point out how 
frequently a diagnosis of malarial fever based upon clinical symp- 
toms alone has proved false, how often a tuberculous, a syphilitic, 
or a septic infection has been overlooked, and termed malaria. It 
will suffice to say that errors of this kind, in view of our present 
knowledge and the ease with which they can be avoided by every 
physician, should no longer occur. The diagnosis of malaria should 
in every case be based upon a microscopic examination of the blood. 

The search for the specific organism, it is true, may be very 
tedious at times, but it will always be crowned with success if the 
disease in question be malaria. Again and again the author has 
seen cases in which the clinical symptoms alone would not have 
warranted the diagnosis of malaria, and in which the true nature of 
the disease was cleared up only by a careful examination of the 
blood; and cases have often been seen in which the diagnosis of 
malaria based upon clinical symptoms alone was disproved by the 
absence of plasmodia from the blood and the post-mortem examina- 
tion. 

While it is true that the life-history of the organism is as vet 
only imperfectly understood, it being still an open question whether 
or not the various forms observed represent different stages in the 
development of one and the same species, this is of no importance 
from a clinical standpoint, and the demonstration in the blood of 
any one of the forms to be presently described will always warrant 
the diagnosis of malaria. 

The parasite in question, as stated above, is a protozoon, and be- 
longs to the class of hsematozoa, representatives of which are found 
in the blood of various animals, such as the rat, frog, tortoise, carp, 
various birds, etc. 

Method of Examination. The necessary amount of blood 
is best obtained by puncture of the lobe of the ear after this has 



THE BLOOD. 89 

been thoroughly cleansed with soap and water and dried. The 
first few drops are wiped away. A small drop of blood is then 
received upon a cover-glass held with a pair of forceps, care being 
taken that the tip of the drop only is touched, when the specimen 
is immediately transferred to a slide. Cover-glasses and slides 
must be absolutely clean, and it is best to keep both in bottles filled 
with alcohol or a mixture of alcohol and ether. If these precau- 
tions be taken and the drop is not too large, the corpuscles will 
spread out in an even layer between the two glasses and retain 
their principal features. Pressure should always be avoided. For 
the examination of the specimens an oil-immersion lens is almost 
indispensable, unless, indeed, the observer has been thoroughly 
trained in hematologic research. 

Whenever the specimens can be examined within one hour after 
their preparation, it is probably always best to use fresh blood. If, 
however, a longer time must elapse, or if it is desired to preserve 
the specimens, dry cover-glass preparations must be employed. 
These are best fixed by immersion for thirty minutes in abso- 
lute alcohol or a mixture of equal parts of absolute alcohol and 
ether, when they may be stained with Chenzinsky-Plehn's solution 
(which see). The specimens should be floated on the solution, and 
allowed to remain for several hours. They are then washed in 
water, dried between filter-paper, and mounted in a drop of balsam. 
The red corpuscles will be colored a light red, the leucocytes blue, 
the eosinophilic granules a deep red, and the parasites blue (Plate 
III., Fig. 4). 

This method, as well as the one presently to be described, may 
also be advantageously employed by the beginner, who may experi- 
ence some difficulty in the recognition of the hyaline forms of the 
organism. 

A drop of a concentrated solution of methylene-blue in 0.6 per 
cent, salt-solution is placed upon the finger and a drop of blood 
allowed to flow directly into this, when it is mounted in the usual 
manner, care being taken that as small a drop as possible, both of 
the staining-fluid and of the blood, be employed. The organisms 
are colored a light blue, while the red corpuscles present their 
normal color. Should any of the latter be also stained, as happens 
at times, the color will be uniform throughout, so that no confu- 
sion can possibly arise between these and the plasmodia. 

The following forms may be found in the blood : 



90 CLINICAL DIAGNOSIS. 

1. Hyaline non-pigmented intracellular bodies. These apparently 
represent the earliest stage in the development of the parasite, and 
are found in all forms of malarial fever, being especially abundant 
during the latter part of the paroxysm or immediately thereafter. 
At first sight they may be mistaken for vacuoles, but upon closer 
investigation it will be found that they exhibit distinct movements 
of an amoeboid character, and may thus be easily recognized with 
a little experience. 

The rapidity with which these changes in the form of the organism 
occur in the tertian type of ague is most astonishing, and sketches 
of any one phase can often, indeed, be made only from memory, 
while in quartan fever the movements are much slower and far less 
extensive. 

In the irregular fever of the sestivo-autumnal form amoeboid 
movements may likewise be observed, but more commonly the 
parasite assumes a ring-like appearance, and does not throw out 
distinct pseudopodia. If these forms be carefully observed, it will 
be found that they are not absolutely quiescent, but alternately 
expand and contract. 

In tertian fever the organism (Plate IV.) is pale and indistinct, 
while in quartan fever it is sharply outlined and somewhat re- 
fractive (Plate V., Fig. 2). In the gestivo-autumnal form the 
organism is usually much smaller than in the tertian type, and 
the ring-like bodies just described frequently present a distinctly 
shaded aspect at some point in their interior which closely re- 
sembles the darker portion in the centre of a normal corpuscle 
(Plate Y., Fig. 1). It is thus possible, even at this stage in the 
development of the parasite, to distinguish between fever of the 
tertian, quartan, and sestivo-autumnal type. 

The numbers in which these small, non-pigmented intracellular 
organisms may at times be met with is most astonishing. In a 
case of pernicious malarial fever of the algid type, which the writer 
had occasion to examine, and in which a history of only one week's 
illness without chills was obtained, normal red corpuscles were in- 
deed only exceptionally found. The case was one of the aBstivo- 
autumnal form of fever. 

2. Pigmented intracellular organisms. These represent a later 
stage in the development of the parasite, and, like the non- 
pigmented intracellular bodies, are met with in all types of 
malarial fever. Their appearance, however, differs considerably 



PLATE IV 



O 













The Parasite of Tertian Fever.. 

i, Normal Red Corpuscle; 2-4, Non-pigmented Stage of the Organism, showing Amoeboid Move- 
merit's; 5-7, Progressive Pigmentation and Growth; S-11, the Process of Segmentation; 12, Young 
Forms; 13, Large Extra-cellular Organism; 14, Mode of Formation of Extra-cellular Body; 15, Small 
Fragmented Extra-cellular Organism; 16, Flagellate Body and Free Flagella. Unstained Specimen. 
(Personal Observation.' 



PLATE V 



FIO. 1. 



O ( 










r* 






c 





Z Schmidt feat 

The Parasite of Aestivo-Automnal Fever, 
i, Normal Red Corpu; radual Growth of the Organism; n and 12, Segmenting Bodies: 

13, Young Forms; 14-22, Crescents, Ovoids and Spherical Bodies, with and without Bib; 23, Flagellate 
Body. Unstained Specimen. (Personal Observation.) 

FIG. 2. 











-it fecti 



The Parasite of Quartan Fe 
I, Normal Red Corpuscle; 2-6, Gradual Growth of the Organism ; -. Pigmented Extra-cellular Body ; 
S. Segmenting Body ; 9, Young Forms ; 10. Vacuolated Extra-cellular Body ; 11, Flagellate Form. Un- 
stained Specimen. (Personal Observati 



THE BLOOD. 9] 

in the various forms, [n tertian fever minute granules of a 
reddish-brown color appear in the bodies of the organism very 

soon after the paroxysm. These gradually increase in Dumber, 
while the invaded corpuscles proportionately become paler and 
paler, until finally only an indistinct shell-like outline can he dis- 
cerned. In fresh specimens the granules, which often assume the 
form of little rods, resembling bacteria, exhibit most active molecu- 
lar movements, attracting attention at once. The body of the para- 
site, which during its development has gradually increased in size, 
is probably hyaline, and may still be seen to undergo amoeboid 
movements. These are not nearly so active, however, as in the 
non-pigmented stage. The movements, moreover, cannot be fol- 
lowed so readily, owing to the presence of the granules. At first 
sight these appear to be scattered in small collections throughout 
the red corpuscle, and the impression may be gained that several 
organisms are present at the same time. Upon closer investiga- 
tion, however, it will be seen that this is only apparently the case, 
and that the granules are confined to the bulbous extremities of the 
pseudopodia of a single parasite. Before the end of forty-eight 
hours the organism has filled out the entire red corpuscle, which 
at the same time has also attained a larger size than normal. The 
amoeboid movements become less and less marked, and the pigment- 
granules, which may still be quite active, tend to collect about the 
periphery. (Plate IV.) 

In quartan fever pigmented intracellular bodies likewise appear 
very soon after the paroxysm. The individual granules, however, 
are somewhat larger, of more irregular size, and darker in color 
than those seen in the tertian type. (Plate V., Fig. 2.) Instead 
of exhibiting active molecular movements, moreover, they are 
almost entirely quiescent, being usually grouped along the periph- 
ery of the organism. While amoeboid movements can at first be 
observed, these become less and less marked, until finally, at the 
end of from sixty-four to seventy-two hours, they have ceased 
entirely. The organism then presents a round or ovoid form, but 
does not fill the red corpuscle entirely. It is curious to note that 
in this form of ague the red corpuscles do not become decolorized, 
but rather darker than normally, and at times specimens may be 
seen which present a distinctly greenish or brassy appearance. 
When the parasite has become fully developed the corpuscle is 
smaller than normally, and upon staining it may be seen that the 



92 CLINICAL DIAGNOSIS. 

organism is still surrounded by a narrow zone of corpuscular pro- 
toplasm, even when this is not apparent in unstained preparations. 

The pigmented intracellular bodies which may be found in sestivo- 
autumnal fever (Plate V., Fig. 1) can be readily distinguished 
from those observed in tertian and quartan ague, as in these forms 
pigment-granules also appear after the paroxysm. They are never 
numerous, however, and often only one or two minute, dark gran- 
ules can be detected near the periphery of the organism. The 
latter, even in the later stages of its development, scarcely ever 
occupies much more than one-third of the corpuscle. Usually the 
granules exhibit scarcely any movements. As in the quartan type 
of ague, decolorization of the red corpuscles does not occur, and 
here, as there, a greenish, brassy appearance is often observed. At 
times the red corpuscles are shrunken, crenated, or spiculated. 

At the beginning and during the paroxysm forms are at times 
seen in which the few pigment-granules that may be present have 
gathered in the centre of the parasite and formed a solid clump. 
From the fact that these are only observed during the paroxysm, 
and that central blocks of pigment are only found during the stage 
of segmentation (see below) in tertian and quartan ague, and from 
the fact that pigment-bearing leucocytes are observed at the same 
time and are likewise only found during the same stage in other 
types of the fever, Thayer and others conclude that these bodies 
are pre-segmenting forms of the parasite. The gradual evolution 
of the non-pigmented intracellular body in sestivo-autumnal fever 
is, however, but imperfectly understood, as the principal changes 
apparently occur in the spleen. In a fatal case of undoubted restivo- 
autumnal fever, however, a large, pigmented intracellular organism, 
much resembling those seen in cases of tertian fever, was found by 
the writer in the spleen. Possibly its presence may be explained 
by assuming the existence of a mixed infection. In the peripheral 
blood only the small, non-pigmented and pigmented intracellular 
organisms described above were found during life, although 
numerous examinations of the blood were made. Just before death 
a crescent was obtained from the blood of the finger. 

3. Segmenting bodies. In cases of tertian and quartan fever the 
progress of segmentation may be directly observed under the micro- 
scope if specimens of blood be obtained just prior to or during 
the chill. In tertian fever organisms will then be seen in which 
the destruction of the red corpuscle has advanced to a stage 



THE BLOOD. 93 

where it is only possible to make out a pale contour of the original 
host. The parasite itself has gradually assumed a granular ap- 
pearance, and the pigment-granules, which until then have ex- 
hibited pronounced molecular movements, now become quiescent, 
larger and rounder, and show a distinct tendency to collect in the 
centre of the body, where they form a roundish mass in which the 
individual components can scarcely be made out. While this 
change in the position of the pigment is taking place, beginning 
segmentation of the surrounding granular protoplasm will be ob- 
served. This at first is most marked at the periphery, from which 
delicate striae will gradually be seen to extend toward the central 
mass, dividing up the protoplasm into a number of oval bodies 
which closely resemble the petals of a flower. (Plate IV.) Still later 
these bodies, which in reality are the sporules of the parasite, will 
be found scattered in an irregular manner throughout the interior 
of the organism. The apparent envelope then disappears, and the 
sporules, which in tertian fever usually number from fifteen to 
twenty, lie free in the blood. Quite frequently, also, a sudden 
expulsion of the little bodies is observed and the impression gained 
as though the envelope had been burst asunder. Upon close in- 
spection, even at the petal stage, it will be seen that almost every 
sporule presents a tiny dot in its interior, which may at first sight 
be mistaken for a pigment-granule, but which in all probability is 
a nucleus. In two cases the writer thinks that he could also make 
out a little cilium at one end of a sporule, but it is possible that 
this was only an accidental appearance. After the expulsion of 
the sporules these are frequently seen to move about in an active 
manner, but sooner or later they come to a rest. 

While the progress of segmentation is very frequently observed 
to proceed in the manner described above, this is not invariably 
the case. It may thus happen that segmentation occurs before the 
pigment-granules have had time to gather at the centre, or that the 
parasitic protoplasm breaks up into sporules directly without the 
intervention of the petal stage. In every case, however, the forma- 
tion of sporules is directly associated with the occurrence of a par- 
oxysm, and represents the process of reproduction of the parasite. 

The ultimate fate of the sporules is as yet unknown, but it is 
likely that they in turn invade new corpuscles, cause their destruc- 
tion, and become segmented, thus giving rise to a new generation. 
As the process of segmentation, moreover, coincides in time with 



94 CLINICAL DIAGNOSIS. 

the occurrence of the chill, it would appear that the interval elapsing 
between two consecutive chills — i. e., the type of the ague — de- 
pends upon the rapidity with which the non-pigniented forms 
arrive at maturity. 

In quartan a^ue the manner in which segmentation takes place 
differs somewhat from that observed in the tertian form. It will 
here be observed that the pigment-granules, which, as has been 
pointed out above, have gathered along the periphery of the organ- 
ism, as the parasite approaches maturity become arranged in a 
stellate manner, and apparently reach the centre through certain 
definite protoplasmic channels. Here they finally form a dense 
clump, and while the protoplasm assumes a finely granular appear- 
ance segmentation proper begins and proceeds as in the tertian 
form. In quartan ague, however, the number of segments is, as a 
rule, smaller, varying between six and twelve. The entire seg- 
menting body, moreover, is smaller than in the tertian form, and the 
segments are arranged in a more symmetrical manner. Here, in- 
deed, the most perfect rosettes are observed. (Plate V., Fig. 2.) 

In aestivo-autumnal fever segmenting bodies are only exception- 
ally seen in the peripheral blood, and it appears that the process of 
reproduction occurs principally in the spleen. The pre-segmenting 
forms, described above, here undergo segmentation in a manner 
closely resembling that observed in tertian fever. The number of 
segments, moreover, is about the same, varying, as a rule, between 
ten and twenty. The segmenting body itself, however, is much 
smaller than in either the tertian or quartan form, and it is not 
possible to distinguish any remains of the original host. 

4. Creseentic, ovoid, and spherical bodies. (Plate V., Fig. 1.) 
These are only observed in cases of aestivo-autumoal fever when 
this has persisted for at least one week. At first sight they 
apparently bear no relation to the other forms which have already 
been described, and it has long been an open question whether 
or not these bodies actually represent a stage in the life-history 
of the common malarial parasite. Grassi and Felerti have ap- 
plied the name Laveriana malarias to this form. More recent 
investigations have rendered it probable that they are directly 
derived from the pigmented intracellular forms. Specimens may 
thus be met with in which crescentic bodies are found in the in- 
terior of red corpuscles that have lost but little of their original 
color. Such observations, however, are not common. The 



THE BLOOD. 95 

typical crescents which are usually seen are highly refractive 

bodies, somewhat larger than a red corpuscle, measuring from 
7 u to J) a in length by 2 n in breadth. Their extremities arc 
usually rounded off and joined by a delicate, curved line bridging 
over their concave border. This is supposed to represent the re- 
mains of the original host. At other times this hood-like appen- 
dage is found along the convex border. The little pigment-gran- 
ules and rods, which are always found in the interior of the ere— 
cents, are generally collected about the centre of the body, although 
they are occasionally also seen in one of the horns. While usually 
quiescent, a migration of some of the granules toward one extremity 
and back to the central mass may at times be observed. The ovoid 
and spherical bodies, which are usually much smaller than the cres- 
cents, exhibit the same general features, however, and are often like- 
wise provided with a little hood. It is supposed by some that the 
spherical bodies develop from the ovoids, and these again from the 
crescents. Like the crescents, the ovoid and spherical forms may 
be found in the interior of red corpuscles. 

5. Extracellular pigmented bodies. In tertian and quartan ague 
some of the pigmented intracellular bodies, instead of undergoing seg- 
mentation when they have arrived at maturity, may be seen to leave 
their hosts and to appear as such in the blood. At the same time 
they increase considerably in size, and in the tertian form may indeed 
become as large as a polynuclear leucocyte. (Plate IV.) The pigment- 
granules, moreover, exhibit an activity in their movements which is 
most astonishing, and never observed under other conditions. The 
outline of the parasite is then usually irregular and quite indistinct. 
Upon careful observation it will be seen that in some of these bodies 
the movements of the granules after awhile become less and less 
marked, and finally cease, while the body of the parasite itself be- 
comes still more irregular in outline. This appearance undoubtedly 
is referable to the death of the organism. In others a gradual frag- 
mentation is observed, small particles of the pigmented mother-sub- 
stance being cut off from the parent-form. It is thus quite common 
to see the original parasite break up into four or five smaller bodies 
in wdiich the movements of the pigment-granules persist for some 
time. Sooner or later, however, these cease, the outlines of the bodies 
become more and more indistinct, and death occurs. In still others 
the formation of vacuoles may be observed, the pigment-granules 
at the same time becoming quiescent. This process is likewise 



96 CLINICAL DIAGNOSIS. 

regarded as one of degeneration. Most interesting, however, is 
the fact that flagellation may occur in some of these extracellular 
forms. It will then be observed that the pigment-granules which 
exhibit a most surprising activity in their movements tend to col- 
lect near the centre of the organism, while at the same time curious 
undulating movements may be made out along its contours. Sud- 
denly one or more (one to six) extremely slender filaments will be seen 
to be protruded from as many points on the periphery, presenting 
minute enlargements here and there in their course. (Plate IV.) The 
length of these filaments, or flagella, as they are termed, varies con- 
siderably. As a rule, it does not exceed the diameter of from five to 
eight red corpuscles, but much larger specimens are at times observed, 
and it appears to the writer that in most illustrations they are 
represented too short. With these flagella the organism exerts 
most active whipping movements, scattering the red corpuscles to 
the right and left. Attention is, indeed, usually first drawn to the 
presence of these bodies by the disturbance which they cause in the 
field of vision. Occasionally one of the flagella may be seen to 
become detached from the body of the parasite and to move about 
among the corpuscles in a rapid, snake-like manner. In micro- 
scopic specimens they gradually come to a rest and often curl into 
a spiral. Their ultimate fate is not known. 

That an error should ever happen in distinguishing such detached 
flagella from the spirilla of relapsing fever seems very improbable, 
as the true nature of these formations is shown by the presence or 
absence of other forms of the malarial organism. 

Beyond the fact that the flagellate organisms in tertian fever are 
larger than in the quartan form, no special points of difference exist. 
(Plate V., Fig. 2.) In sestivo-autumnal fever similar changes may 
be observed in the crescents, ovoids, and spherical forms. In 
crescents it is thus not at all uncommon to observe a small hyaline 
protrusion from the surface of the organism, which may later be- 
come detached. This process was formerly regarded as one of 
regeneration, but it is questionable whether this is actually the 
case. In other specimens, again, true fragmentation, or vacuoliza- 
tion, may occur, and flagellate bodies are met with in this type of 
fever as well as in tertian and quartan ague. The flagellates, as 
in quartan fever, are smaller than those observed in the tertian 
form, but other points of difference do not exist. (Plate V., Fig. 1 .) 

From the above description it will be seen that three forms of 



THE BLOOD. 97 

the malarial parasite may be found in the blood, viz., the parasite of 
tertian, quartan, and sestivo-autumnal fever, and it has been shown 
that these three forms may be readily distinguished from each other. 
It should be mentioned, however, that in tertian and quartan fever 
several groups of the same organism may be present at one time, 
and as the process of segmentation coincides with the occurrence of 
a paroxysm, it will be readily seen that the number of paroxysms 
within a given time depends directly upon the number of groups 
which may be present in the blood. If a double infection with the 
tertian parasite has occurred, one group of organisms may thus have 
just reached the segmenting stage, while the second group has only 
attained a twenty-four hours' growth, the result being that maturity 
is reached by the two groups on successive days. Quotidian fever 
is then the result. Should still more groups be present, the clinical 
picture will accordingly become more complicated. In quartan 
ague, similarly, double quartan fever will occur if two groups be 
present, and triple quartan fever if three groups be present at one 
time. 

In conclusion, it may not be out of place to refer to the presence 
of pigment-bearing leucocytes in the blood of malarial patients. 
These are quite constantly met with during the paroxysm, and it is 
indeed often possible to observe the process of phagocytosis directly 
under the microscope (See Fig. 12.) The forms which are taken 
up are the central pigment-clumps of organisms that have under- 
gone sporulation, the small, fragmented extracellular forms, the 
flagellate bodies, and even the segmenting bodies. In every case 
where pigment-bearing leucocytes — which are probably always of 
the neutrophilic, polynuclear variety — are observed malarial fever 
should be suspected and a careful examination made, as a melan- 
semia has so far only been observed in this disease, in relapsing 
fever, and in connection with the rare melanotic tumors, in which 
not only leucocytes containing melanin occur in large numbers, 
but also masses of this pigment float free in the blood. 

FILARIASIS. 

Pilaria sanguinis hominis (Lewis), syn., filaria Wuchereri (da 
Silva Lima); filaria Bancrofti (Cobbold); filaria Mansoni; trichina 
cystica (Salisbury); trichina sanguinis hominis nocturna (Manson). 

Several varieties of the parasite (Fig. 24), which belongs to the 

7 



98 



CLINICAL DIAGNOSIS. 



class of nematodes, have been observed in the blood of man. Among 
these are filaria sanguinis hominis nocturna, filaria sanguinis hom- 
inis diurna, or filaria sanguinis hominis, var. major, and filaria san- 
guinis hominis, var. minor. 

The female of filaria nocturna, according to Manson's description, 
is " a long, slender, hair-like animal, quite three inches in length, 
but only one one-hundredth inch in breadth, of an opaline appear- 
ance, looking as it lies in the tissues like a delicate thread of catgut, 
animated and wriggling. A narrow alimentary canal runs from 
the simple club-like head to within a short distance of the tail, the 
remainder of the body being almost entirely occupied by the repro- 
ductive organs. The vagina appears about one twenty-fifth of an 
inch from the head; it is very short and bifurcates into two uterine 



Fig. 24. 




Filaria sanguinis hominis. (After Lewis. 



horns, which, stuffed with embryos in all stages of development, 
run backward nearly to the tail." (Osier.) The male worm is 
rarely seen, and is much smaller than the female. While the adult 
parasite has its habitat in the lymphatics, the embryos, which are 
set free in enormous numbers, invade the blood-current, in which 
they may readily be found at night; during the day an examination 
of the blood will usually yield negative results. This periodicity 
may, however, be reversed by having the patient sleep in the day- 
time and be about at night. Each embryo has an envelope of its 
own, which is hyaline in appearance and within which the young 
worm, measuring 0.34 mm. in length by 0.0075 mm. in breadth, 
is able to extend and contract itself. In fresh preparations these 
organisms are readily detected by the disturbance which their 
movements create among the corpuscles, when they are apparently 
transparent and homogeneous, but after some time, when the worm 



THE BLOOD. 99 

has come to rest, it will be Been thai they arc granular and trans- 
versely striated. 

As the mere presence of these parasites usually does not produce 
symptoms, and as an examination of the blood made in daytime, 
as already stated, generally yields negative results, attention is only 
drawn to their presence when symptoms pointing to an occlusion 
somewhere in the course of the lymphatic channels exist, as evi- 
denced by chyluria (which see), elephantiasis, or lymph scrotum. 

DISTOMIASIS. 

Bilharzia haernatobia (Cobbold), syn., gynaecophorus (Diesing); 
distomum hsemotobium (Bilharz); schistosoma (Weinland); distoma 
capense (Harley); thecosoma (Maguin-Taudon.) 

The Bilharzia haernatobia belongs to the class of trematode pla- 
todes, and has never been met with in the United States or in 
Europe. According to Bilharz, the greater portion of the Fellah 
and Coptic population of Egypt is infected by it, giving rise to 



Fig. 25. 




Bilharzia haernatobia. Male and female, with eggs. (v. Jaksch.) 

diarrhoea, haematuria, and ulceration of the mucous surfaces. The 
male is smaller but thicker than the female, measuring from 12 to 
14 mm. in length; on its abdominal surface a deep groove is found 
with overlapping edges, which serves for the reception of the female 
(Fig. 25). 

While the adult parasite is but rarely seen in the blood, its ova 
are frequently detected. These are slender bodies, measuring 0.12 
mm. in length by 0.04 mm. in breadth, and provided with a distinct 
little spike-like projection, issuing from one extremity or the side. 



100 



CLINICAL DIAGNOSIS. 



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CHAPTEE II. 

THE SECRETIONS OF THE MOUTH. 

SALIVA. 

Normal saliva is a mixture of secretions derived from the sub- 
maxillary, sublingual, parotid, and mucous glands of the mouth. 
It is a colorless, inodorous, tasteless, somewhat stringy and frothy 
liquid, and serves the purpose of aiding in the acts of mastication, 
deglutition, and digestion. Its amount per diem varies from 600 
to 1200 grammes. 

General Characteristics. 

Normal saliva has a specific gravity of from 1.002 to 1.009, cor- 
responding to the presence of from 4 to 10 grammes of solids. Its 
reaction is usually slightly alkaline; it may, however, become acid 
at times, when lactic acid fermentation takes place in the mouth. 
This acid, according to Magittot, corrodes the enamel of the teeth, 
and may ultimately produce dental caries. 

Chemistry of the Saliva. 

In order to give an idea of the general composition of the saliva 
the following analyses are appended, the figures corresponding to 
1000 parts by weight : 



Water 


995.2 


994.20 


988.1 


Ptyalin 1 


1.34 


1.30 


1.3 


Mucin \ 
Epithelium > 


1.62 


2.20 


2.6 








Fatty matter .... 






0.5 


Sulphocyanides 


0.06 


0.04 


0.09 


Alkaline chlorides . 


0.84 






Disodium phosphate 


0.94 


2.20 


3.4 


Magnesium and calcium salts . 


0.04 






Alkaline carbonates 









These figures are too high, as they refer to the total precipitate obtained with alcohol. 



102 CLINICAL DIAGNOSIS. 

In order to demonstrate the presence of the sulphocyanides it is 
usually only necessary to heat a few e.c. of the pure saliva, faintly 
acidified with hydrochloric acid, with a dilute solution of perchlo- 
ride of iron, when a red color will be seen to develop. If necessary, 
larger quantities, such as 100 c.c., are evaporated, and the test ap- 
plied to the concentrated fluid. Of organic matter a little albumin, 
mixed with mucin, and about 1 gramme of urea pro litre are found. 
Of all these substances, the ptyalin is especially interesting from a 
physiologic point of view. It may be prepared in a pure state, 
according to Gautier's method: 

To a large quantity of saliva alcohol (98 per cent.) is added as long 
as a flocculent precipitate is seen to form. This is collected upon a 
small filter and dissolved in a little distilled water. The solution 
thus obtained is treated with several drops of a solution of bichloride 
of mercury, in order to remove albuminous material, which is filtered 
off. The excess of mercury is removed by means of sulphuretted 
hydrogen, when the remaining liquid is evaporated at a temperature 
of from 35° to 40° C, and taken up with strong alcohol. The in- 
soluble residue is dissolved in a little water, filtered, dialyzed in 
order to remove inorganic salts, and finally precipitated with strong 
alcohol, when ptyalin will separate out in light flakes. Obtained 
in this manner ptyalin is a white, amorphous substance, soluble in 
water, dilute alcohol, and glycerine. In neutral or even slightly 
alkaline solutions, but not in acid solutions, ptyalin rapidly trans- 
forms boiled starch into dextrin and sugar at a temperature of from 
35° to 40° C. This transformation takes place according to the 
equation : 

10C 6 H 10 O 5 + 4H 2 = 4C 12 H 22 O n - C 6 H 10 O 5 + C 6 H 10 O 5 

Starch. Maltose. Achroodextrin. Erythrodextrin. 

In order to test for the presence of ptyalin a few c.c. of saliva are 
filtered and added to a solution of starch; the mixture is placed in 
the warm chamber for some time, when it is tested with sulphate 
of copper or iodine. At first, starch gives a blue color with iodine; 
after the reaction has proceeded further a red or violet-red color is 
obtained, indicating the presence of erythrodextrin, while no change 
in color at all results when achroodextrin only is present. The 
maltose may be recognized by the fact that it turns the plane of 
polarization more strongly to the right than glucose; it also reduces 
Fehling's solution, and may thus be recoguized in the absence of 
glucose. 



THE SECRETIONS OF THE MOUTH. 



103 



The test for nitrites, which may likewise be present in the saliva, 
is conducted in the following manner: About 10 c.c. of saliva are 
treated with a few drops of Tlasvay's reagent and heated to a b m- 
perature of 80° C, when a red color will develop in the presence 
of nitrites. The reagent is prepared as follows: 0.5 gramme <>f 
sulphanilie acid in 150 c.c. of dilute acetic acid, and 0.1 gramme of 
naphtylamin are dissolved in 20 c.c. of boiling water. After stand- 
ing for some time the supernatent fluid is poured off from the blue 
sediment, treated with 150 c.c. of dilute acetic acid and kept in a 
sailed bottle. 



Microscopic Examination of the Saliva. 

If normal saliva be allowed to stand, two layers will be seen to 
form, viz., an upper clear and a lower cloudy layer, which latter 
contains certain morphologic elements. Among these salivary cor- 
puscles, pavement epithelial cells, and micro-organisms are found. 
(Fig. 2G.) 

Fig. 26. 




Buccal secretion (eye-piece III., obj. Reichert, 1/15. homogeneous immersion ; Abbe's mirror, 
open condensers). Friedliinder's and Giinther's method (v. Jaksch). a, epithelial cells ; 
b, salivary corpuscles ; c, fat-drops ; d, leucocytes , e, spiroctueta buccalis ; /, comma-bacillus of 
mouth ; g, leptothrix buccalis ; h, i, k, various fungi. 

The salivary corpuscles resemble white corpuscles very closely, 
but differ in their greater size and coarser appearance. The epithe- 
lial cells found in the saliva are large, irregular, polygonal cells, 
provided with well-defined nuclei and nucleoli; they exhibit certain 
irregularities in size according to their origin, and belong to the 
class of pavement or stratified epithelium. 

Micro-organisms. While schizomyeetes and moulds are only 
exceptionally found in the mouth under normal conditions, and are 



104 CLINICAL DIAGNOSIS. 

then undoubtedly derived from ingested food, bacteria are always 
present in large numbers, and it cannot be surprising that all forms 
which are found in the air, food, and drink may here be encoun- 
tered. (Plate VI. . Fig. 1.) Some of these, such as leptothrix buc- 
calis innominata, bacillus buccalis maxim us, leptothrix buccalis 
maxima, iodococcus vaginatus, spirillum sputigenum, and spiro- 
chete dentium, are always present. Together with other bacteria 
these have been found in carious teeth, in abscesses communicating 
with the mouth and pharynx, and in exudates on the mucous mem- 
branes of these parts. In all probability, however, they are non- 
pathogenic. In this connection it is interesting to note that in con- 
tradistinction to the bacteria which are only temporarily found in 
the mouth the majority of those which are constantly present can- 
not be cultivated on artificial media. 

Important from a practical standpoint is the fact that a number 
of pathogenic micro-organisms may at times be found under normal 
conditions. The diplococcus pneumoniae, also known as the pneu- 
mococcus of Fraenkel and Weichselbaum, the diplococcus lanceo- 
latus, the micrococcus lanceolatus, the micrococcus septicaemia? sputi, 
and the micrococcus pneumonia? cruposa? (Sternberg), has thus been 
fonnd in a virulent condition in from 15 to 20 per cent, of healthy 
individuals, and it is even claimed that in a non- virulent state it is 
constantly present in the mouth. Streptococci are likewise fre- 
quently observed, but usually possess but little virulence or none 
at all when obtained from the healthy mouth and tested upon ani- 
mals. Pyogenic staphylococci may also be found at times, but are 
far less common than the streptococci. Most important is the occa- 
sional occurrence of the diphtheria bacillus in the mouth in indi- 
viduals who have not been exposed to contagion. Welch 1 mentions 
that virulent organisms were found by Park and Beebe in the 
healthy throats of eight out of 330 persons in Xew York, who 
gave no history of direct contact with cases of diphtheria. Two 
of these eight persons later developed the disease. Xon-virulent 
bacilli were found in twenty-four individuals of the same series, 
and the pseudo-diphtheria bacillus in twentv-seven. Other patho- 
genic bacteria which may be found in normal mouths are the 
micrococcus tetragenus, the bacillus pneumonia? of Friedlander, 
the bacillus crassus sputigenus, and the bacillus coli communis. 

1 Dennis' System of Surgery : Surgical Bacteriology. 



PLATE VI 



FIC. 1 



* ^^ 



Sf 




mm 



Bacteria of the Mouth. (Cornil Babes.) 



FIG. 2. 




Leptothrix Bueealis. (v. Jaksch.) 



THE SECRETIONS OF THE MOUTH. [05 

It is interesting to aote that the secretions of the mouth and 

throat, as most secretions of the body, possess a certain degree of 

germicidal power. The staphylococcus aureus, the streptococcus 

pyogenes, the micrococcus tetragenus, the typhoid bacillus, and the 
cholera spirillum, when present in moderate numbers, are thus 

killed by the saliva. The diphtheria bacillus, however, is far more 
resistent, and may survive for twenty-four to forty days. It has 
been found as a matter of fact that the organism may be demon- 
strated in the throats of some individuals who have passed through 
an attack of diphtheria, during several weeks after all the clinical 
symptoms have disappeared. The diplococcus pneumoniae is even 
said to grow well in saliva, although it rapidly loses its virulence. 
By then cultivating it upon pneumonic sputum, however, the viru- 
lence of the organism is again restored. The individual bacteria 
will be considered in detail later on. 

Pathologic Alterations. 

It has been mentioned that from 600 to 1200 c.c. of saliva are 
secreted in the twenty-four hours. This quantity varies under 
certain conditions. An increase is thus frequently noted in preg- 
nancy, in various neurotic conditions, in inflammatory diseases of 
the mouth, in dental caries following the administration of pilo- 
carpus, in poisoning with mercury, acids, and alkalies. The quan- 
tity is diminished in all febrile diseases, in diabetes, and often in 
nephritis. The effect of psychic emotions upon the secretion of 
saliva as well as of other glands is well known, an increase or 
decrease in the flow being produced under various conditions. 

In determining whether or not salivation actually exists the 
physician should not only be guided by the statements of his 
patient, but an actual estimation of the amount secreted within a 
definite period of time should be made. Hysterical individuals not 
infrequently complain of "salivation," when a direct estimation 
will show that the amount of saliva is not only not increased, but 
actually diminished. 

Among qualitative changes may be mentioned an increase in the 
amount of urea, which has been repeatedly observed, especially in 
nephritis. 

Urea may be demonstrated as follows: The saliva is extracted 
with alcohol, the filtrate evaporated, and the residue dissolved in 



J06 CLINICAL DIAGNOSIS. 

amyl alcohol. This is allowed to evaporate spontaneously, when 
crystals of urea will separate out, and may then be examined micro- 
scopically and chemically. (See Urine.) 

Bile-pigment and sugar have thus far never been found in the 
saliva. 

Of drugs, potassium iodide and potassium bromide rapidly pass 
into the saliva. Upon this property the indirect examination of the 
gastric juice as to its digestive power — i. e. 9 the presence or absence 
of free hydrochloric acid — by means of the potassium iodide and 
fibrin packages of Giinzburg, is partly based. 

In order to test for potassium iodide strips of filter-paper moist- 
ened with starch solution are immersed in the saliva acidified with 
nitric acid: in the presence of potassium iodide the starch-paper 
will turn blue. 

The Saliva in Special Diseases of the Mouth. 

Catarrhal Stomatitis. In this affection the quantity of saliva is 
increased. Microscopically an increased number of epithelial cells 
and many leucocytes are noted, their number depending upon the 
intensity of the morbid process. 

Ulcerative Stomatitis. In this condition, following mercurial 
poisoning or scurvy, the same appearance is noted microscopically as 
in simple stomatitis. In addition there may be observed necrotic 
tissue, red blood-corpuscles, and innumerable leucocytes. The reac- 
tion of the saliva is intensely alkaline, its color markedly brown, 
and its odor fetid. 

G-onorrhoeal Stomatitis. The number of cases of gonorrhoeal 
stomatitis that have thus far been observed is small. The disease, 
however, has as yet received but little attention, and is probably 
more common than is generally supposed. In the adult it may 
be contracted through coitus contra naturam, while in the newborn 
the infection is undoubtedly brought about in the same manner as 
the corresponding disease of the conjunctiva. In suspected cases 
the exudate which forms upon the gums, the tongue, and the palate 
should be examined for the presence of gonococci. In adults the 
organism has thus far not always been found; in the newborn, how- 
ever, Rosinski has succeeded in demonstrating its presence in all 
cases examined. 

Thrush. Oidium albicans (Fig. 27) is mostly observed in chil- 



THE SECRETIONS OF THE MO UTIL 



107 



dren, but may also occur in adults, and especially in phthisical in- 
dividuals, sometimes lining the whole mouth. If in such a case a 
bit of the membrane be pulled off and examined microscopically, it 
will be found to consist of epithelial cells, leucocytes, and granular 
detritus, with a network of branching, band-like formations, which 



Fig. 27. 




03 



O'idium albicans, the vegetable parasite of muguet or thrush. 
(Reduced from Ch. Robin.) 



present distinct segments. The contents of the segments are clear, 
and usually contain two highly refractive granules — the spores, one 
of which is situated at each pole. These segments diminish in size 
toward the end of each band, their contents at the same time becom- 
ing slightly granular. 

TARTAR. 

In a bit of tartar scraped from the teeth actively moving spiro- 
chetal are seen, as well as long, usually segmented bacilli, frequently 
forming bands which are colored a bluish-red by a solution of iodo- 
potassic iodide. Leptothrix buccalis, shorter bacilli which are not 
colored by the above reagent, micrococci, and a large number of 
leucocytes and epithelial cells which have undergone fatty degene- 
ration are also found. 



COATING OF THE TONGUE. 

A brown coating of the tongue is often observed in severe infec- 
tious, diseases, consisting of remnants of food and incrustated blood. 
Microscopically, in addition to a large number of epithelial cells, 
enormous numbers of micro-organisms and a large number of dark, 



108 CLINICAL DIAGNOSIS. 

cell-like structures, probably derived from desquamated epithelial 
cells, are found. The white coating of the tongue contains epithe- 
lial cells in large numbers, many micro-organisms, and a few sali- 
vary corpuscles. 

TUBERCULOSIS OF THE MOUTH. 

In cases of lupus and the so-called benign form of tuberculosis 
of the mouth it is rarely possible to demonstrate the presence of 
tubercle bacilli, even in scrapings taken from the base of the ulcers, 
or in the diseased tissue itself, while in cases of ulcerative disease 
associated with phthisis in its advanced stages they may be fre- 
quently found in large numbers. In some cases, however, their 
demonstration is by no means easy. In the saliva they are only 
exceptionally seen. 

ACTINOMYCOSIS. 

In cases of actinomycosis it is occasionally possible to demon- 
strate the presence of the specific organism in or about carious teeth. 
More commonly, however, the patients are not seen until the primary 
symptoms of the disease have disappeared, when the typical kernels 
can no longer be found at the original points of entry or have be- 
come unrecognizable owing to calcification and retrogressive changes. 

Usually the disease has already progressed to the formation of a 
distinct tumor or abscess, and it may then be necessary to make 
an exploratory incision and to examine the scrapings which are 
brought away. The number of kernels which may be found is at 
times very small, but a careful examination will probably always 
lead to their detection if the disease in question be actinomycosis. 

COATING OP THE TONSILS. 

Pharyngomycosis Leptothrica. 

In the props met with in the crypts of the tonsils in cases of 
follicular tonsillitis, as also in persons who have had frequent 
attacks of tonsillitis, according to Chiari, epithelial cells and long, 
segmented fungi — the leptothrix buccalis (Plate VI., Fig. 2) — which 
are colored bluish-red with a solution of iodo-potassic iodide, are 
seen. At times patches composed of these fungi extend over a con- 



THE SECRETIONS OF THE MOUTH 109 

aiderable area oi' the tonsil.-, so that it may be doubtful whether or 
not the disease be a beginning diphtheria. A microscopic exami- 
nation, however, will in such cases settle all doubts. 

Diphtheria. 

Recognizing the great importance of an early diagnosis in such a 
dreaded disease as diphtheria, an examination for Loftier' s bacillus 
in doubtful case- has become just as important to-day as that for 
the bacillus of tuberculosis, and every physician .should make him- 
self familiar with the methods employed for its recognition. 

By means of a sterilized, stout platinum loop, a pair of forceps, 
or a cotton swab, a piece of membrane is scraped from the tonsils, 
the soft palate, or the pharynx and at once transferred to a steril- 
ized test-tube, closed with a pledget of cotton. A particle of the 
membrane is then spread in as thin and uniform a layer as possible, 
upon a cover-glass, by means of the platinum loop or forceps, which 
have been previously passed through the flame of a Bunsen burner. 
When dry the specimen is fixed by being passed through the flame 
three or four times, when it is ready for staining. For this purpose 
Loffler's alkaline solution of methylene-blue, which consists of 30 
c.c. of a concentrated alcoholic solution of methylene-blue in 100 c.c. 
of an aqueous solution of potassium hydrate (1 : 10,000), may be 
advantageously employed, the specimen being stained for from five 
to ten minutes. It is then rinsed in water, placed on a slide, the 
excess of water removed with filter-paper, and examined with a 
one-twelfth oil-immersion lens. 

A dahlia methyl-green solution may likewise be employed. This 
consists of 10 grammes of a 1 per cent, aqueous solution of dahlia- 
violet and 30 grammes of a 1 per cent, aqueous solution of methyl- 
green. The specimen is stained for from one to two minutes. 

If it is desired to employ Gram's method, the specimen is most 
conveniently stained for three minutes with a freshly prepared con- 
centrated alcoholic solution of gentian-aniline water. This is pre- 
pared by adding aniline oil to 10 c.c. of distilled water, drop by 
drop, thoroughly shaking after the addition of each drop, until the 
solution becomes opaque. It is then filtered and treated with 10 
c.c. of absolute alcohol and 11 c.c. of a concentrated alcoholic solu- 
tion of gentian-violet. The specimen is decolorized in a solution 
composed of 1 gramme of iodine and 2 grammes of potassium 



110 CLINICAL DIAGNOSIS. 

iodide, dissolved in 300 c.c. of water. After remaining in this 
solution for five minutes the specimen is rinsed in alcohol and the 
process repeated until the violet color disappears. It is then trans- 
ferred to absolute alcohol, oil of cloves, and mounted in balsam. 

Cultures should also be made, preferably upon a mixture of blood- 
serum and bouillon, as recommended by Loftier. This is composed 
of three parts of blood-serum and one part of bouillon, containing 
10 per cent, of peptone, 3 per cent, of grape-sugar, and 0.5 per cent, 
of sodium chloride, the mixture being solidified in the usual manner. 
Upon this medium Loftier' s bacillus grows so much more rapidly 
than other organisms usually present in the secretions of the mouth 
and throat that at the end of twenty-four hours they often form 
the only colonies that attract attention. Should other colonies of 
similar size be present these are generally quite different in appear- 
ance. In this manner a diagnosis can be made upon the day fol- 
lowing the inoculation of the tube. 

In the absence of blood-serum bouillon, alkaline bouillon, nutrient 
gelatin, nutrient agar, glycerine-agar, and potato may be employed. 
Coagulated egg-albumin, as pointed out by Booker, and milk are 
also good soils. 

The colonies are large, round, elevated, and grayish- white in 
color, with a centre that is more opaque than the slightly irregular 
periphery. The surface of the colony is at first moist, but after a 
day or two assumes a dry appearance. 

Fig. 28. 




a 

Bacillus of diphtheria. (Abbott.) 

a. Its morphology when cultivated on glycerine agar-agar. b. Its morphology as seen in 

cultures on Loffler's hlood-serum. 



The bacillus (Fig. 28) is non-motile and varies in size and shape, 
its average length being from 2.5 /j. to 3 fi, its breadth from 0.5 // 
to 0.8 fi. Its morphologic characteristics are so peculiar as to 
render its identification upon cover-slip preparations and in sections 
of the diphtheritic membrane an easy matter in most cases. 



THE SECRETIONS OF THE MOUTH. \ \ \ 

Sometimes the organism appears as a straight or slightly curved 

rod; especially characteristic, however, are irregular and often 
bizarre forms, such as rods with one or both ends terminating in 

a little knob, and rods broken at intervals, in which short, well- 
defined round, oval, or straight segments can be made out. 

Some forms stain uniformly, others in an irregular manner; the 
most common present the appearance of deeply stained granules in 
faintly stained bacilli. 

Streptococci are also seen, as a rule, and it may be said that the 
gravity of a case is directly proportionate to the number of strepto- 
cocci present. 

It is important to note that diphtheria bacilli may still be found 
in the throat for weeks after all clinical symptoms have disap- 
peared. Patients should hence be isolated until a bacteriologic 
examination has demonstrated the absence of the organism. 



CHAPTER III. 

THE GASTRIC JUICE AND GASTRIC CONTENTS. 

THE SECRETION OP GASTRIC JUICE. 

The gastric juice is the result of the glandular activity of the 
stomach, and the only secretion of the digestive tract which pre- 
sents an acid reaction. 

As is well known, the mucous membrane of the stomach is covered 
throughout its entire extent by a single layer of cylindrical epithe- 
lium, which dips down in places to line the orifices and larger ducts 
of the numerous tubular glands with which it is beset. Of these 
latter, two kinds have been described, viz., the fundus and pyloric 
glands, so named from the location at which they are principally 
found. In the secretory portion of a fundus gland two different 
sets of cells can be distinguished, one being small, granular, and 
polyhedral or columnar, bordering upon the narrow lumen of the 
tube, termed chief or principal cells by Heidenhain; they are also 
known as central or adelomorphous cells. These stain with aniline- 
dyes to only a slight extent. The others, known as parietal, delo- 
morphous, or oxyntic cells, are variously situated between the adelo- 
morphous cells and the membrana propria, being most numerous in 
the necks of the glands. They are larger than the chief cells, oval 
or angular and finely granular in structure, possessing a strong 
affinity for the aniline-dyes. The pyloric glands, which are found 
only in the region of the pylorus, on the other hand, are character- 
ized by the greater length of their ducts, which are also lined by 
the cylindrical epithelium of the mucous membrane proper. The 
secretory portion of these glands is represented by a single layer 
of short and finely granular, columnar cells, which closely resem- 
ble the chief cells of the fundus glands. In addition to these a 
few isolated cells, the cells of Nussbaurn, are found, which in 
structure and in their behavior to aniline-dyes resemble the pari- 
etal cells. 

Upon chemical examination the gastric juice is seen to consist 



THE QASTRIQ JUICE AND GASTRIC CONTENTS. ] \:) 

essentially of water, free hydrochloric acid, pepsin, rennet (a milk- 
curdling ferment*, mucus, and certain mineral salts. 

Of these constituents free hydrochloric acid is secreted by the 
parietal cells, pepsin and the milk-curdling ferment by the chief 
cells of the fundus and the pyloric glands, while the mucus is the 
product of the cylindrical goblet-cells lining the stomach and the 
wider portions of its glandular ducts. 

It must be borne in mind, however, that the ferments mentioned 
do not exist in the cells as such, but as zymogens, which are trans- 
formed into the ferments through the activity of the free hydro- 
chloric acid. According to modern investigations, moreover, the 
zymogens only are secreted by the cells. 

Until recently it was supposed that the gastric juice is only 
secreted upon appropriate stimulation of the nervous mechanism 
of the stomach, either directly or indirectly, and that the stomach 
in its quiescent state — I. e., when not digesting — is empty. The 
researches of Schreiber and Martius, however, have rendered the 
correctness of this view very doubtful, as they were able to obtain 
quantities of gastric juice, varying from 1 to 60 c.c, from the non- 
digesting stomach of every normal person examined;* and the 
writer, likewise, has never failed to obtain a few c.c. under the 
same conditions. 

TEST-MEALS. 

Although the secretion of gastric juice takes place continuously, 
the amount that can usually be obtained from the non-digesting 
organ is not sufficient for analytical purposes. It is, therefore, 
necessary to stimulate the glandular apparatus of the stomach to 
increased activity. This may be accomplished with thermic, chem- 
ical, electric, and digestive stimuli, among which the last named 
are the most convenient and the most effective, furnishing a picture 
not only of the chemical, but also of the motor and resorptive 
activity of the organ. The analytical results will, however, depend 
to a large extent upon the character of the food ingested, starches 
and fats exerting but a slight stimulating effect, while proteids 
cause a copious secretion of gastric juice. The ingestion of fluids 
at the same time will likewise influence the results obtained, owing 
to the dilution of the gastric juice. The time of the height of 
digestion, moreover, varies with the kind and quantity of food 
taken. In order to obtain uniform results it is, therefore, neces- 

8 



114 CLINICAL DIAGNOSIS. 

sary to withdraw the gastric contents at a certain period after the 
ingestion of a meal of known composition and bulk. 

Numerous test-meals have been proposed. The following are 
the most important: 

The Test-breakfast of Bwald and Boas. 

This consists of from 35 to 70 grammes of wheat-bread and from 
300 to 400 c.c. of water or weak tea without sugar. It is best to 
give this meal to the patient early in the morning when the stomach 
is empty — i. e., as a breakfast. The gastric contents are obtained 
one hour later. 

The Test-dinner of Riegel. 

This consists of a plate of soup (400 c.c), a beefsteak (200 
grammes), a slice or two of wheat-bread (50 grammes), and a 
glassful of water (200 c.c). The contents of the stomach are 
obtained after four hours. The disadvantage of this method lies 
in the fact that the lumen of the stomach-tube is frequently occluded 
by large pieces of undigested meat, a source of annoyance which 
may be guarded against, however, by making use of finely chopped 
meat. 

The Double Test-meal of Salzer. 

For breakfast the patient receives 30 grammes of lean, cold roast, 
hashed or cut into strips sufficiently small as not to obstruct the 
stomach-tube, 250 c.c of milk, 60 grammes of rice, and one soft- 
boiled egg. Exactly four hours later the second meal is taken, 
consisting of 35-70 grammes of stale wheat-bread and 300-400 c.c. 
of water. The gastric contents are withdrawn one hour later. In 
his manner the gastric juice is not only obtained at the height of 
digestion, but an idea may at the same time be formed of the motor 
power of the stomach. Under normal conditions the organ should 
contain no remnants of the first meal at the time of examination. 

The Test-breakfast of Boas. 

This consists of a plateful of oatmeal- soup, prepared by boiling 
down to one pint a quart of water to which one tablespoonful of 
rolled oats has been added. A little salt may be used if desired, 
but nothing more. The contents of the stomach are obtained one 




THE GASTRIC JUICE AND GASTRIC CONTENTS. \ \ :, 

hour later. This best-meal was devised by Boas in order to guard 
against the introduction from without of lactic acid, which is present 
in all kinds of bread. The meal is employed in doubtful eases of 
cancer of the stomach in which a quantitative estimation of lactic 
acid is to be made, the stomach being washed out completely the 
night before. 

Still other test -meals have been suggested, but they do not pos- 
sess any material advantage over those described. 

THE STOMACH-TUBE. 

The stomach-tubes which are now generally in use are essentially 
large Xelaton catheters. They should measure at least from 72 to 
75 cm. in length, and be provided with three fenestra, of which 
one is placed at the end of the tube and two laterally, as near the 
end as possible. For the purpose of washing out the stomach the 
tube is connected with a glass funnel by means of ordinary rubber 
tubing, which can be detached from the stomach-tube proper. 
There is no advantage in rubber funnels or in having a continuous 
tube. 

It is important that the tubes should be thoroughly cleansed in 
hot water as soon after use as possible. The advice of Boas, more- 
over, to have special marked tubes for tuberculous, syphilitic, and 
carcinomatous patients should be borne in mind. Patients in whom 
lavage is to be practised for any length of time should provide their 
own instruments. 

Contraindications to the Use of the Tube. 

Of direct contraindications to the use of the tube there should be 
mentioned the existence of the various forms of valvular disease 
when in a state of imperfect compensation, angina pectoris, arterio- 
sclerosis of high degree, aneurism of the large arteries, recent hem- 
orrhages from whatever cause, marked emphysema with intense 
bronchitis, acute febrile diseases, etc. 

The Introduction of the Tube. 

The technique of the introduction of the tube should be as simple 
as possible; the exhibition of complicated bottle-arrangements for 



116 



CLINICAL DIAGNOSIS. 



Fig. 2£ 



the purpose of obtaining the gastric juice only adds to the excite- 
ment of a nervous patient, and should be avoided. The patient's 
clothing and floor of the room should be protected from being soiled 
by material that may be vomited along the sides of the tube, the 
dribbling of saliva, etc. For this purpose Turck's rubber bib with 
pouch may be advantageously employed. " It is so arranged as to 
form a pouch in front to catch the saliva or stomach-contents that 

may be thrown off from the mouth or 
stomach. A detachable tube passes from 
the bottom of the pouch and is conducted 
into a basin or any vessel." 1 

Cocainization of the pharynx is rarely 
necessary, but may be resorted to in hy- 
persesthetic individuals, a 10 per cent, 
solution being employed. 

The tube, held like a pen, is intro- 
duced to the posterior wall of the pharynx, 
the patient bending his head forward, 
and not backward, as is usually advised. 
The patient is then told to swallow, but 
this is not absolutely necessary. The 
tube is pushed on until resistance is felt 
when it meets with the floor of the stomach. 
The entire process does not occupy ten 
seconds. At the least sign of cyanosis, 
or of marked pallor, the tube should be 
withdrawn at once and the patient ob- 
served for a day or two before a second 
attempt is made. 

If the gastric juice does not flow at 
once, the patient is instructed to bear down with his abdominal 
muscles, and, if this be insufficient, to cough a little. Eepeated 
attempts of this kind will usually bring about the desired result, 
unless the tube has not been introduced far enough or too far; in 
the latter case it will double upon itself, so that its end may actually 
stand above the level of the liquid. (Method of expression.) 2 

Aspiration must at times be employed. For this purpose Boas' 
bulbed tube (Fig. 29) is most convenient. The manner in which it 




Boas' bulbed tube. 



1 Manufactured by G. Tiemann & Co., New York. 

- Pressing upon the abdomen with the hands is of no object. 



THE GASTRIC JUICE A X I > <;.\STRIC CONTEXTS \ 17 

is n>c(\ is the following: The proximal end of the tube, after having 
been introduced into the stomach, is compressed and the bulb 
squeezed, when the distal end is clamped and the bull) allowed to 
expand. When this is repeated several times a partial vacuum is 
produced in the tube, which usually causes a flow of gastric juice. 
In the absence of such an instrument the stomach-tube may be con- 
nected with a bottle in which a partial vacuum has been established 
by aspiration (Fig. 30). Unless the patient is accustomed to the 
introduction of the tube these more complicated apparatus should 
be avoided as much as possible. (Method of aspiration.) 

The writer has fouud that in cases in which gastric juice cannot 
be obtained by expression the. flow may often be started by suction 
with the mouth, and he regards this method as preferable to the 
one just described. With due precautions, viz., holding the tube 
between the fingers near the mouth of the patient, so as to be in- 
formed at once, by the sense of touch, when the stomach contents 
have reached this point, unpleasant results will be obviated. If 
only a very small amount of gastric juice is present in the stomach 
— i. e., when a definite flow cannot be established — it is best to suck 
lightly with the mouth, to compress the tube firmly, to remove it as 
rapidly as possible, and empty it into a little dish. A few drops 
sufficient to test for free hydrochloric acid can thus always be 
obtained, even from the non-digesting organ. 

Einhorn's bucket-method is of little value, as the amount of gastric 
juice wldch can be obtained is entirely insufficient for analytical 
purposes. It may be employed, however, in patients who are par- 
ticularly nervous and object to the use of the tube, and possibly, 
also, when its use is contraindicated. The test for hydrochloric 
acid can be made, but the amount of information which can thus be 
obtained is in itself of comparatively little importance. 1 

In order to wash out the stomach the fuunel-tube is attached, the 
funnel filled with lukewarm water or any desired medicated solu- 
tion, elevated to a height somewhat above the head of the patient, 
and the water allowed to flow. From 500 to 1000 c.c. may be 
introduced at one time. By suddenly depressing and inverting 
the funnel, over a suitable vessel, before all water has left the 
funuel, a siphon arrangement is established and the stomach emp- 
tied. It is well to measure the returning water as well as the 

1 For a description of this method the reader is referred to Einhorn's article in the Twentieth 
Century Practice, vol. viii. Wra. Wood &. Co. 



118 



CLINICAL DIAGNOSIS. 



amount introduced. Should the flow diminish or cease before all 
the water has been removed, the end of the tube probably stands 
above the level of the liquid, and the flow can be started again by 
pushing the tube on further or by withdrawing it a little, as the 
case may be. 



Fig. 30. 




Arrangement of bottle for the aspiration of the gastric contents. 

Washing out the stomach soon after the ingestion of a full meal 
is always very tedious and annoying if not an impossible pro- 
cedure, as the fenestra readily become obstructed. Should this 
occur, the funnel, filled with water, is elevated as high as possible, 
with a view to overcome the obstruction by hydrostatic pressure, 
or, if this prove insufficient, the funnel-tube is detached and the 
obstruction dislodged by means of air, for which purpose a Politzer- 
bag or the bulb of a Boas' tube is very convenient. 



GENERAL CHARACTERISTICS OP THE GASTRIC 

JUICE. 

Pure gastric juice is an almost clear, faintly yellowish fluid, of 
a sour taste and a peculiar, characteristic odor. Its specific gravity 
varies between 1.002 and 1.003, corresponding to the presence of 
but 0.5 per cent, of solids. Its reaction, owing to the presence of 
hydrochloric acid, is acid. 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 119 

AMOUNT. 

Very little is known of the total quantity of gastric juice secreted 
in the twenty-four hours. The figure given by Beaumont, viz., 
180 grammes pro die, based upon observations made upon the often- 
quoted Canadian hunter, Alexis St. Martin, is undoubtedly too low. 
The amount given by Bidder and Schmidt, viz., that corresponding 
to about one-tenth of the body- weight, is probably more correct. 1 
It may be stated a priori, however, that the quantity secreted varies 
within wide limits, being influenced by numerous factors and notably 
by the degree of the appetite and the amount and character of the 
food taken, especially that of the proteids. The age and sex of the 
individual, the time of day, notably in its relation to the ingestion 
of food, the emotions, etc., undoubtedly influence the glandular 
activity of the stomach. 

From the non-digesting organ, as has been pointed out, from 1 to 
60 c.c. of gastric juice may be obtained at one time. The amount 
which can be procured during the process of digestion, on the other 
hand, varies with the amount of liquid ingested, the time of expres- 
sion, the size and motor power of the stomach, and the degree of 
transudation; the process of resorption probably does not play any 
part, as it has been ascertained that very little water, if any, is 
absorbed by the stomach. 

According to Boas, from 20 to 50 c.c. of filtrate can be obtained 
exactly one hour after the ingestion of Ewald's test-breakfast under 
physiologic conditions. 

Abnormally large quantities of gastric juice are practically only 
found in cases of so-called hypersecretion, the " Magensaf tfl uss " of 
the Germans, which may occur periodically or continuously. For- 
merly the presence of gastric juice in appreciable quantities in the 
non-digesting stomach was regarded as conclusively proving the 
existence of this disease, but in the light of Schreiber's researches 
this position can no longer be maintained. The diagnosis should, 
hence, only be made when in conjunction with the clinical symp- 
toms of hypersecretion from 100 to 1000 c.c. of pure gastric juice 
can be obtained from the non-digesting organ. To this end the 
stomach should be emptied completely by the tube before retiring, 

1 Griinewald's figure— i. e., 1580 grammes— the author likewise regards as too low. The daily 
secretion appears to vary between 2000 and 3000 c. c. 



120 



CLINICAL DIAGNOSIS. 



and an examination made upon the following morning, no food or 
liquids being allowed in the meantime. 

In various pathologic conditions abnormally large quantities of 
liquid may be obtained, which cannot, however, be regarded as 
gastric juice. Attention will be drawn to these conditions at 
another place. 

CHEMICAL EXAMINATION OP THE GASTRIC JUICE. 



Chemical Composition of the Gastric Juice. 

As has been briefly shown above the gastric juice consists of water, 
free hydrochloric acid, certain ferments, their zymogens, and mineral 
salts. Analyses giving the exact chemical composition of pure, 
uncontaminated gastric juice in man are still wanting, owing to 
the difficulty of excluding the saliva. In patients the subjects of 
gastric fistula analytical studies have, however, repeatedly been 
made, and from the table below, taken from Schmidt, an idea may 
be formed of the various amounts of solid constituents contained in 
1000 parts of gastric juice uncontaminated by food or the products 
of ^digestion, but not free from saliva: 



Water . 
Solids . 

Organic material . 
Sodium chloride 
Calcium chloride . 
Potassium chloride 
Ammonium chloride 
Hydrochloric acid . 
Calcium phosphate ] 
Magnesium phosphate r 
Iron phosphate i 



994.40 
5.60 
3.19 
1.46 
0.06 
0.55 



0.20 



0.12 



The Acidity of the Gastric Juice is Referable to the 
Presence of Free Hydrochloric Acid. 

It has been conclusively demonstrated by Schmidt that the acidity 
of the gastric juice is due to the presence of free hydrochloric acid. 
After accurately determining the amount of chlorine and all basic 
substances present, it was found that after all of the latter had been 
saturated a quantity of hydrochloric acid still remained, which in 
the dog varied between 0.25 and 0.42 per cent., with an average 



////: GASTRIC JUICE AND GASTRIC CONTENTS. 



121 



of 0.33 per cent The amount of free acid was also determined by 
titration and the same results reached as by gravimetric analysis. 

While the acidity of pure gastric juice — /. c, gastric juice not con- 
taminated by saliva or food in its various stages of digestion — is 
thus solely due to the presence of free hydrochloric acid, other 
factors enter into consideration in the examination of the gastric 
contents during the process of digestion. Acid salts and varying 
amounts of lactic acid derived from the carbohydrates of the food 
are also found. At the beginning of digestion the acidity, accord- 
ing to Ewald, is due to a certain extent to the presence of lactic 
acid. 1 Hydrochloric acid, it is true, is present at the same time, 
but is held in combination by albuminous material. Later on, 
when the albuminous affinities have become saturated, it appears as 
such, with the result that the formation of lactic acid progressively 



Fig. 31. 



P.M 
3.0 



2.0 
1.5 
L25 

1.0 
0.75 



0.5 



0.25 





























.-r-"" ~°^>s^ 


^ N ^ __ ... ... 


V^ 


yr- ' 


*'■ 


X 


/ 


/ 








/ 


/ 


/ 


r 


/ 


/ 


i 




4 -, 7 " V 




T / _ _ _ "^ 




/ '-' S 




j f 




\i 


fi 


e 







10 20 30 40 50 60 7.0 80 90 100 

Illustrating the curve of acidity after Ewald's test-breakfast. (Rosenheim.) 

Hydrochloric acid. Lactic acid, x Beginning of the stage of free hydrochloric 

acid. P M. Pro mille. The numbers upon the abscissa indicate the minutes. 

diminishes, owing to the inhibitory action on the part of the hydro- 
chloric acid upon the lactic-acid-producing organisms. The varying 
degrees of acidity after such test-meals as those of Ewald and 



See Lactic Acid, p. 153. 



122 



CLIXICAL DIAGXOSIS. 



Kiegel, at different periods of digestion, and the amount of the two 
acids present, may be seen from the accompanying diagrams (Figs. 
31 and 32). 



Fig. 32. 













1 


III 


P.M. 












1 












! | 














1 


4.C 












i 1 1 1 






















1 1 1 1 1 




















3.5 






i 








i 








1 i 








1 








) i 




3.0 




! 




























| 








i ■ 1 — -1 vj 








_^ 


"v 










1 I i -J^' 














\ 1 1 >k 














■ y< \ 














/ 1 










2.0 




y 1 






























1 s\ 
































x ' 






1.5 




. 1/ 






/' i 1 










INI 1 1 1 1 1 








/ „ 


_ 








' 


1.0 


/ ' 






'""- 


--^ i 1 


A i 










^v. 






/ / 


















/ l x 












^-^ 






/ V 
















0.5 




Mill 








n 














i / 












/ 1 1 






'/ \ ■ \ 1 ! ■ 1 , 1 1 





30 60 90 120 "150 180 210 240 270 300 

Illustrating the curve of acidity after Riegel's test-breakfast. (Rosenheim.) 

' Hydrochloric acid. Lactic acid. X Beginning of the stage of free hydrochloric 

acid. 

Under pathologic conditions the amount of free hydrochloric acid, 
as will be shown, may undergo great variations, diminishing on the 
one hand to zero, and increasing on the other to 0.5 per cent., or even 
more. At the same time the amount of lactic acid, which normally 
is present in very small amounts, and is absent altogether at the 
height of digestion, may greatly increase. Fatty acids, moreover, 
which are normally not present in the gastric juice, mav also be 
observed in pathologic conditions. It is thus seen that the total 
acidity of the gastric juice, especially in disease, cannot be regarded 
as indicating the amount of one single acid, unless the absence of 
abnormal acids, lactic acid, and acid salts is insured. 

Method of Determining- the Total Acidity of the Gastric 

Contents. 

To this end a known quantity of gastric juice is titrated with a one- 
tenth normal solution of sodium hydrate, using phenolphthalein as an 



THE GASTRIC JUICE AND GASTRIC CONTENTS. L23 

indicator, when the number of c.c. of the one-tenth norma] solution 
employed, multiplied by the equivalent of 1 c.c. of this solution in 
terms of hydrochloric acid, will indicate the amount of acid present 
in terms of the latter, from which the percentage-acidity is readily 
calculated. 

A normal solution of sodium hydrate is one containing the equiva- 
lent of its molecular weight in grammes — i. c, 40 grammes, in 1000 
c.c. of distilled water; a decinormal solution will, therefore, con- 
tain 4 grammes in the same volume of water. This quantity is 
dissolved in less than 1000 c.c. and the solution brought to the 
proper strength by titrating it with a solution of oxalic acid of 
known strength. 

From the equation, 

2NaOH + C 2 HA = C 2 Na 2 0, + 2H 2 0, 
it is seen that two molecules of NaOH (mol. weight 40) combine 
with one molecule of C 2 H 2 4 -f- 2H 2 (mol. weight 126), or 4 parts 
by weight of the former with 6.3 of the latter. One-tenth gramme of 
oxalic acid would, hence, require 15.873 c.c. of the one-tenth normal 
solution of XaOH for its neutralization, as is apparent from the 
equations: 

6.3 : 1000 : : 0.1 : x ; 6.3x = 100 and x = — = 15.873 

6.3 

One-tenth gramme of pure, crystallized oxalic acid is dissolved in 
distilled water, and the solution titrated with the one-tenth normal 
solution of sodium hydrate which is to be corrected, using two or 
three drops of a 1 per cent, alcoholic solution of phenolphthalein as 
an indicator, until the rose color of the solution has entirely dis- 
appeared; 15.9 c.c. should bring about this result. As the NaOH 
solution, however, has been purposely made too strong, less will be 
required. The amount of water that must then be added in order 
to bring the solution to its proper strength is determined by the 

formula C = - — , in which C represents the number of c.c. of water 

which must be added to the remaining solution, N the total number 
of c.c. remaining after one titration, n the number of c.c. consumed 
in one titration, and d the difference between the number of c.c. 
theoretically required and that actually used in one titration. The 
solution having thus been properly diluted, the correctness of its 
strength is again tested and a further correction made, if necessary, 
until absolute accuracy has been attained. 



124 CLINICAL DIAGNOSIS. 

1000 c.c. of the one-tenth normal solution containing 4 grammes 

of XaOH are equivalent to 3.65 grammes of HO, as is seen from 

the equation: 

NaOH - HC1 = Nad - H 2 

4^ 36.5 

1000 c.c of the - 1 - normal solution represent 3.65 grins, of HCL 
100 " " " " " " 0.365 grm. " " 

10 « « " « " " 0.0365 " gt " 

1 " " (i " " represents 0.00365 " " «■ 

Application to the gastric juice: 5 or 10 c.c. of the filtered gastric 
juice are titrated with the one-tenth normal solution of sodium 
hydrate, using two or three drops of a 1 per cent, alcoholic solu- 
tion of phenolphthalein as an indicator, until the rose color which 
appears after the addition of every drop of the sodium hydrate solu- 
tion no longer disappears on stirring or becomes deeper after the 
addition of a further drop. The number of c.c. of the one-tenth 
normal solution employed multiplied by 0.00365 will then indicate 
the acidity of the 5 or 10 c.c. of gastric juice in terms of HO, from 
which the percentage-acidity is readily calculated. 

Example: 10 c.c. of gastric juice required the addition of 6.5 c.c. 
of the one-tenth normal solution; 6.6 X 0.00365 (i. e., 0.0237) 
would hence indicate the acidity of the 10 c.c. of gastric juice in 
terms of HC1, and 0.0237 X 10 = 0.237, the percentage-acidity. 

As these figures express only the amount of HC1 in pure gastric 
juice obtained from normal individuals, it has been found more 
convenient for clinical purposes to indicate merely the degree of 
acidity by the number of c.c. of the one-tenth normal solution 
employed. In the above example, in which 6.5 c.c. of the latter 
were used, the percentage-acidity would thus be indicated by the 
figure 65; t. e., the number of c.c. of the one-tenth normal solution 
necessary to neutralize 100 c.c. of gastric juice. 

Under normal conditions figures varying from 40 to 60 are usually 
found one hour after the ingestion of Ewald's test-breakfast, while 
in pathologic conditions considerable variations are observed. It 
may be stated, as a general rule, that in the acute and chronic in- 
flammatory conditions of the stomach, as well as in some of the 
neuroses, the acidity of the gastric contents is below normal. 
Higher figures are met with in cases of ulcer, in some cases of 
dilatation, and especially frequently in some of the neuroses, in 
which a degree of acidity corresponding to 90 or even more is not 
infrequently observed. Increased acidity, usually associated with 



THE GASTRIC JUICE AND GASTRIC CONTENTS. L25 

hypersecretion of gastric juice, is met with in the so-called hyper- 
8€cretio acida et oontintta of Reichmann. 

It has been pointed out that the reaction of normal gastric juice 
i- always acid, owing to the presence of free IIC1, and the same 
may be said to hold good for the gastric contents in general obtained 
frmn a normal individual. Pathologically an acid reaction is also 
the rule, as in those cases in which HC1 is absent fatty acids and 
lactic acid in considerable amount usually make their appearance. 
It is, therefore, not at all surprising that an alkaline, neutral, or 
amphoteric reaction is but rarely, or, at least, not commonly, ob- 
served in the gastric contents artificially obtained, and practically 
only seen in the so-called mucous form of chronic gastritis. In 
vomited material such observations are quite common, not so much 
so, however, in the specimens first brought up as in those that are 
subsequently ejected. The vomited material in cases of so-called 
vomitus matutimis, which is usually referable to a chronic catarrhal 
condition of the pharynx, generally presents an alkaline reaction, 
owing to the fact that the fluid brought up is largely unchanged 
saliva. 

The Source of the Hydrochloric Acid. 

That the HC1 is not directly derived from the chlorides ingested 
is shown by the fact that it is still secreted by a starving animal. 
The same point is also proved by the observations of Schreiber, 
which go to show that the secretion of HC1, as indicated above, is 
continuous, not to mention the well-known fact that material free 
from chlorine, when ingested, will cause the secretion of an acid 
gastric juice. It is apparent, then, that the chlorides of the blood 
must furnish the necessary chlorine, and as the pyloric glands, 
which contain no parietal cells, furnish an alkaline, and the fundus 
glands, which do contain parietal cells, an acid secretion, it is 
thought that these parietal cells are in some manner concerned in 
the production of the HC1. The exact manner in which this takes 
place has not been definitely ascertained, but it is not at all improb- 
able that the HC1 results from a " Masseneinwirkung " on the part 
of carbonic acid, which is present in large quantities in the blood as 
such, upon the sodium chloride, and that, owing to a specific action 
on the part of the parietal cells, the hydrochloric acid is secreted 
iuto the ducts of the glands of the stomach, while the sodium car- 
bonate formed at the same time is returned to the blood. 



126 CLINICAL DIAGNOSIS. 

Two factors are thus necessary in order that a normal amount of 
HC1 should be secreted — L e. } a normal condition of the blood and 
a normal condition of the cells. Whenever the integrity of either 
of these two factors becomes impaired it is clear that an abnormal 
secretion of HC1 or none at all will result. The nervous system, 
furthermore, must be taken into consideration as a third factor, as, 
according to our present knowledge, normal innervation is the sine 
qua non for the normal activity of any organ. The secretion of 
HC1 is impaired whenever the nutrition of the cells of the stomach 
suffers, whether this be the result of inflammatory lesions, new 
growths, or hypera?mic conditions of the stomach, the effect of renal, 
hepatic, or pulmonary diseases, etc., or in consequence of central or 
peripheral nervous influences. 

In the secondary dyspepsias, then, the result of renal, hepatic, 
cardiac, or hsemic diseases, etc., an examination of the gastric juice 
for free HC1 is of comparatively little value from a diagnostic point 
of view, although it may suggest valuable points for the dietetic 
treatment of such patients. 

Significance of the Free Hydrochloric Acid. 

It was formerly thought that the principal function of the stomach 
was a digestive one, and that in the stomach, owing to the action of 
hydrochloric acid and pepsin, albumins were, to a large extent, 
transformed into peptones and albumoses. As pepsin is active onlv 
in the presence of a free acid, it was thought, moreover, that the 
power of the hydrochloric acid to render pepsin physiologically 
active constituted its entire field of usefulness. 

It had already been noted one hundred years ago, however, 
by the Abbe Spalanzani that pieces of meat immersed in gastric 
juice resisted the process of putrefaction for days, and when it was 
shown later on that the free mineral acids ranked among the most 
powerful of antiseptics, and that the stomach secreted an amount 
of free hydrochloric acid sufficient to prevent the development of 
most of the putrefactive organisms, the time had come to doubt the 
correctness of the view previously held. 

Numerous experiments have been made in order to test the anti- 
septic and germicidal power of the gastric juice. Among the more 
important results achieved the following may be mentioned : The 
comma-bacillus of cholera Asiatica is destroved by the normal acid 



THE QASTRIQ JUICE AND GASTRIC CONTENTS, 127 

gastric juice, while infection results when this has been previously 
neutralized — a most important observation. Tin- same holds good 
for numerous other pathogenic organisms which are of special in- 
terest to the clinician. Among these maybe mentioned the various 

species of streptococcus, staphylococcus pyogenes aureus, the bacillus 
of anthrax, etc. Unfortunately, however, not all species of patho- 
genic organisms are destroyed by the acid of the gastric juice, and 
the spores of some of those, moreover, that are destroyed are pos- 
sessed of a considerable degree of resistance. This is especially true 
of the tubercle-bacillus and in many cases of the spores of the 
anthrax-bacillus. 

Those bacteria also which cause lactic acid and butyric acid fer- 
mentation resist the anti-fermentative power of the gastric juice to 
a certain extent, as may be concluded from the fact that they are 
•always present in the intestines. At the beginning of the process 
of gastric digestion, when the hydrochloric acid secreted is imme- 
diately taken up by the albuminous bodies present, traces of lactic 
acid can usually be demonstrated in the gastric contents if carbo- 
hydrochlorates have been ingested. Later on, when free hydro- 
chloric acid appears, lactic acid fermentation ceases. This observa- 
tion is in perfect accord with the fact that the action of the lactic 
acid producers is prevented by the presence of 0.7 p. m. of free HC1. 

From what has been said it may be argued that as the principal 
function of the stomach consists in the furnishing of an antiseptic 
and germicidal fluid, under suitable conditions life could go on in 
the absence of the stomach. That this is possible has actually been 
demonstrated by Czerny, who succeeded in removing almost the 
entire organ from a dog. Five to six years later the same animal 
was killed in Lud wig's laboratory, and it was found at the autopsy 
that " near the cardia a small portion of the stomach had remained, 
surrounding a globular cavity filled with food." This dog then 
had lived for almost six years practically without a stomach, had 
gained in weight, and was to all intents and purposes as healthy 
an animal as one provided with an entire organ. In human beings 
the subjects of carcinoma of the stomach, not the entire organ, it is 
true, but a considerable portion has been removed by operation, 
with the result that the patients enjoyed perfect health as far as 
could be ascertained, notwithstanding the fact that the remainder 
of the organ was incapable of secreting gastric juice. It is very 
probable, then, that the stomach, so far as the process of diges- 



128 CLINICAL DIAGNOSIS. 

tion is concerned, is not absolutely necessary for the maintenance 
of life. 

It has, furthermore, been demonstrated that a deficient secretion 
of HC1 is noted in all cases in which an increased degree of intes- 
tinal putrefaction occurs, and while indol, phenol, and skatol, as 
well as their compounds with sulphuric acid, in the amounts 
observed in physiologic and pathologic conditions, are not thought 
to exert any toxic influence upon the body, it must be admitted 
that the observations were made upon animals, and that the results 
obtained may not be directly applicable to the human being. While 
a single large dose may not produce symptoms, moreover, it is not 
to be inferred that a continuous intoxication with the products of 
intestinal putrefaction may not lead to decided pathologic results. 

The Amount of Free Hydrochloric Acid. 

Pure gastric juice, according to Ewald, Szabo, and Boas, contains 
from 2 to 3 p. m. of free HC1. 

In the digesting organ such amounts are met with at the height 
of digestion only after all albuminous and basic affinities have been 
saturated. The time at which free HC1 can be demonstrated in the 
gastric contents after the ingestion of a meal will, hence, vary with 
the character of the food and its amount. When but little work is 
to be accomplished, free HC1 is found much sooner than otherwise. 
After Ewald' s test-breakfast, for example, free HC1 appears after 
thirty-five minutes, the point of maximum acidity being reached 
after from fifty to sixty minutes, corresponding to the presence 
of 1.7 p. m. Following Riegel's meal, on the other hand, free 
HC1 appears after 135 minutes and reaches its highest point, corre- 
sponding to 2.7 p. m., in from 180 to 210 minutes. (Figs. 31 and 32.) 

Clinically it is necessary to distinguish between euchlorhydria, or 
the secretion of a normal amount of free HC1 (0.1 to 0.2 per cent.), 
hypochlorhydria, or the secretion of a deficient amount of free HC1 
(less than 0.1 per cent.), hyperchlorhydria, in which more than 0.2 
per cent, is found, and, finally, anachlorhydria, in which no HC1 at 
all is secreted. 

Euchlorhydria. Euchlorhydria, when associated with clinical 
symptoms pointing to gastric derangement, is most commonly ob- 
served in nervous dyspepsia. A chronic gastritis can always be 
excluded in the presence of a normal amount of free HC1, thus 



THE GASTRIC JUICE AND GASTRIC CONTEXT-. [29 

constituting :i most important point in the differential diagnosis 
between these two conditions, which can but rarely be definitely 

made from the clinical symptoms alone. A normal secretion of free 
HC1 is, furthermore, observed in some cases of atony or hypatony 
of the muscular walls of the stomach. 

Hypochlorhydria. Hypochlorhydria is associated with all those 
diseases in which the secretory elements have been more or less 
damaged, as iu subacute and chronic gastritis, in some cases of ulcer 
of the stomach or the duodenum, in incipient carcinoma, dilatation, 
and atony. 

Anachlorhydria. Not many years ago it was thought that the 
absence of free HC1 from the gastric contents was pathognomonic of 
carcinoma of the stomach. This view, however, was soon aban- 
doned, as it was shown that cases of carcinoma occur in which HC1 
is not only present, but present in excessive amounts. This is true 
especially of those cases iu which the malignant growth has started 
upon the base of an old ulcer. It was, furthermore, shown that 
anachlorhydria exists in almost all cases of advanced chronic gas- 
tritis, and is a very common occurrence in neurasthenic and hys- 
terical individuals, constituting the so-called hysterical anacidity. 

Hyperchlorhydria. The existence of hyperchlorhydria is gen- 
erally indicative of a gastric neurosis, and is thus frequently met 
with in its simplest form in certain neurasthenic individuals. Asso- 
ciated with a continuous hypersecretion of gastric juice it consti- 
tutes the neurosis that has been described under the term hyperse- 
cretio acida et continua. Hyperchlorhydria is also of frequent 
occurrence in cases of gastric ulcer, and may even occur in carci- 
noma, notably in those cases in which, as has been stated above, 
the new growth has started from an old ulcer. 

Test for Free Acids. 

Following a physical examination of the gastric contents, and, if 
acid, a determination of the general acidity, the next step will be 
to determine whether or not the acid reaction is referable to the 
presence of a free acid, of combined acids, or of acid salts. 

The Congo-red Test. Congo-red is a carmine-colored powder, 
while its solutions are of a peach- or brownish-red color, which 
changes to azure-blue upon the addition of a free acid, but remains 
unaffected in the presence of an acid salt. Congo-red may be em- 

9 



130 CLINICAL DIAGNOSIS. 

ployed in solution or in the form of a test-paper, which latter, how- 
ever, is less delicate than the solution, indicating the presence of 
0.01 per cent, of HC1, while a positive reaction can still be obtained 
with the aqueous solution in the presence of 0.0009 per cent, of free 
HC1. The solution to be employed should be moderately dilute. 
The test-paper is prepared by soaking filter-paper, free from ash, in 
this solution, drying and cutting it into suitable strips. In order to 
test for the presence of a free acid it is only necessary to immerse 
a strip of the test-paper in the filtered gastric juice, or to add a 
drop or two of the solution to a small amount of the juice, when in 
the presence of free acid a blue color will develop, which varies 
from a sky-blue to a deep azure, according to the amount present. 

A negative result will at once exclude the possibility of peptic 
activity, as pepsin acts only in acid solutions. 

If, however, the result of the test be positive, the nature of the 
free acid must still be ascertained, and it is, therefore, necessary to 
test for free HC1, for lactic acid, and for certain fatty acids. 

Tests for Free Hydrochloric Acid. 

The various reagents which may be employed are given below 
arranged according to their degree of delicacy, viz. : 

1. Dimethyl-amido-azo-benzol . . . . 0.02 p.m. 

2. Phloroglucin- vanillin 0.05 

3. Resorcin 0.05 

4. Methyl- violet 0.2 

5. Tropseolin 00 0.3 

6. Emerald-green 0.4 

7. Mohr's reagent 1.0 

The Dimethyl-amido-azo-benzol Test. This test has recently 
been introduced by Topfer, and to judge from his observations, as 
well as from the author's experience, is destined soon to replace the 
phloroglucin-vanillin and resorcin tests in the clinical laboratory. 
The reagent may also be employed in the direct estimation of the 
amount of free HC1 present. The delicacy of the reagent is such 
that the neutral yellow color of the indicator is changed to a reddish 
tinge upon the addition of but one drop of a one-tenth normal solu- 
tion of HC1 in 5 c.c. of distilled water. Organic acids yield a red 
color only when present in amounts exceeding 0.5 per cent.; but 
even then a negative reaction is obtained, if as in the stomach small 
quantities of albumin, peptones, and mucin are at the same time 



THE GASTRIC JUICE AND GASTRIC CONTEXTS. 131 

present. A positive reaction can then only be obtained when 
organic acids are present in amounts far exceeding 0.5 per cent. 
Loosely combined HC1 and acid salts do not produce this change 
in color. Its superior delicacy, as compared with the phloroglucin- 
vanillin and resorcin tests, is apparent from the fact that 5 c.c. of a 
0.5 per cent, solution of egg-albumin, to which six drops of a one- 
tenth normal solution of HC1 have been added, still give a positive 
reaction with dimethyl-amido-azo-benzol, while the phloroglucin- 
vanillin and resorcin reactions are negative. 

For practical purposes a 5 per cent, alcoholic solution is em- 
ployed. One or two drops of this are added to a trace of the gastric 
contents, which need not be filtered : in the presence of free HC1 a 
beautiful cherry-red color develops, which varies in intensity accord- 
ing to the amount of free HC1 present. A test-paper, prepared by 
soaking strips of filter-paper, free from ash, in the 0.5 per cent, 
solution and allowing them to dry, may also be employed. With 
gastric juice containing no free HC1, as with distilled water, a 
yellow color results, the fluid at the same time becoming cloudy 
and beautifully fluorescent. 

The Phloroglucin- vanillin Test. The solution employed con- 
tains 2 grammes of phloroglucin and 1 gramme of vanillin, dis- 
solved in 30 c.c. of absolute alcohol: a yellow color results, which 
gradually turns a dark golden-red, changing to brown when ex- 
posed to light. The solution should, therefore, be kept in a dark- 
colored bottle. Lenhartz suggests using separate solutions of phlo- 
roglucin and vanillin, one or two drops of each being employed in 
the test. Boas recommends a solution of the phloroglucin and 
vanillin in the proportions indicated in 100 grammes of 80 per 
cent, alcohol as still more sensitive and more stable. If a few 
drops of gastric juice, or even of the unfiltered gastric contents, 
containing 0.05 or more per cent, of free HC1, be treated with the 
same number of drops of the reagent, no change in color results, 
while upon the application of gentle heat — boiling and rapid evapo- 
ration are to be avoided — a rose-tint or exceedingly fine rose-colored 
lines develop, which are characteristic of the presence of free HC1. 

For practical purposes it is best to carry on this slow evaporation 
upon a thin porcelain butter-dish, the porcelain cover of a crucible, 
or in a small evaporating-dish of the same material. The color 
obtained in the presence of free HC1 is a rose color in every case, 
varying in intensity with the amount of acid present. A brown, 



132 CLINICAL DIAGNOSIS. 

brownish-yellow, or brownish-red color always indicates that exces- 
sive heat has been applied or that free HC1 is absent. 

Organic acids never produce this reaction; it is not interfered 
with bv their presence, or by albumins, peptones, or acid salts, 
which may occur in the gastric contents. 

A phloroglucin- vanillin test-paper, prepared by soaking strips of 
filter-paper, free from ash, in the solution and drying them, may 
also be employed. If a strip of this be moistened with a drop of 
gastric juice and gently heated in a porcelain dish, as already de- 
scribed, the rose-red color will be seen to develop in the presence 
of free HC1, and does not disappear upon the addition of ether. 

The Resorcin Test. The solution consists of 5 grammes of 
resublimed resorcin and 3 grammes of cane-sugar dissolved in 100 
grammes of 94 per cent, alcohol. It is of equal delicacy as the 
phloroglucin-vanillin solution and has, besides, the advantage of 
greater stability. 

Five or six drops of gastric juice are treated with three to five 
drops of the reagent and slowly evaporated to complete dryness 
over a small flame, when a beautiful rose- or vermilion-red mirror 
will be obtained, which gradually fades on cooling. If the reagent 
be employed in the form of a test-paper, a violet color at first de- 
velops, which upon the application of heat turns brick-red and does 
not disappear upon the addition of ether. 

The presence of acid salts, organic acids, albumins, or peptones 
does not interfere with the reaction. 

The methyl-violet and emerald-green tests cannot be recom- 
mended, as they are uncertain and may lead to error. 

The Tropaeolin Test. Tropaeolin 00, when emploved according 
to the method suggested by Boas, is a very reliable reagent, indicating 
the presence of 0.2 to 0.3 per cent, of free HC1. Three or four 
drops of a saturated alcoholic solution of tropaeolin 00, which has a 
brownish-yellow color, are placed in a small porcelain dish or cover 
and allowed to spread over the surface. A like amount of gastric 
juice is then added and likewise allowed to flow over the surface of 
the dish; upon the application of gentle heat beautiful lilac or blue 
stripes appear, which are said to be absolutelv characteristic of free 
HC1. 

A tropaeolin test-paper may also be prepared by soaking filter- 
paper, free from ash, in the alcoholic solution for some time, and 
then drying and cutting it into strips. A few drops of gastric juice 



THE GASTRIC JUICE AND GASTRIC CONTENTS. \:\:\ 

containing free HC1 produce a more or less pronounced brown color 
upon this paper, which turns lilac or blue upon the application of 
gentle heat. Organic acids, when present in large amounts, like- 
wise produce a brown color, which disappears, however, upon the 
application of heat, and a lilac or blue color never results. 

For ordinary purposes this test is sufficient, and recourse need 
only be had to the more delicate reagents when a negative or a 
doubtful result is obtained. 

Mohr's Test, as Modified by Ewald. Two c.c. of a 10 per 
cent, solution of potassium sulphocyanide are treated with 0.5 c.c. 
of a neutral solution of ferric acetate and diluted to 10 c.c. with 
distilled water, a ruby-red solution resulting. Of this a few drops 
are placed in a porcelain dish, and a drop or two of the filtered gas- 
tric contents allowed to come slowly into contact with the reagent. 
In the presence of free HC1 a light violet color develops at the point 
of contact between the two fluids, which turns a deep mahogany- 
brown upon mixing. 

The test is not interfered with by the presence of acid salts or 
peptones, but is not sensitive enough for practical purposes. 

The Benzopurpurin Test. Benzopurpurin 6B has been highly 
recommended by v. Jaksch as a very sensitive test for HC1. It is 
best used in the form of a test-paper, prepared by soaking strips of 
filter-paper, free from mineral ash, in a concentrated watery solu- 
tion of the reagent and allowing them to dry. 

In the presence of more than 0.4 gramme of HC1 in 100 c.c. of 
gastric juice the dark-red color of the test-paper immediately turns 
a deep blackish-blue. Should a brownish-black color develop, it is 
likely due to the presence of organic acids, or a mixture of these 
and HC1. If the color be caused by organic acids only, it will 
disappear upon washing the strip with a little neutral ether, and 
the original color of the test-paper be restored; but if due to a 
mixture of the two, the reaction is less marked, and does not dis- 
appear. According to Hellstrom, 0.39 milligramme of HC1 dis- 
solved in 6 c.c. of water can be recognized by the addition of only 
5 milligrammes of benzopurpurin. 

Acid salts, peptones, and serum-albumin do not seriously inter- 
fere with the reaction. 

Benzopurpurin test-paper v. Jaksch claims to be more sensitive 
than the Congo-red paper. 



134 CLINICAL DIAGNOSIS. 

The Combined Hydrochloric Acid. 

It has been stated (see p. 122) that the determination of the total 
acidity of the gastric juice can only be referred to HC1 when organic 
acids and acid salts are absent. At the same time the free acid is 
titrated together with the loosely combined. The presence of free 
hydrochloric acid in normal amounts implies, of course, the existence 
of peptic activity, and indicates that all albuminous affinities have 
been saturated. From a practical standpoint, however, in the ab- 
sence of free HC1 it is most important to know whether or not 
hydrochloric acid is secreted — i. e., whether peptic digestion is at a 
standstill or whether an amount is secreted that is only sufficient 
to saturate certain albuminous affinities without appearing in the 
free state. In the treatment of the various forms of gastric dis- 
ease, more especially those associated with an absence of free HC1, 
accurate knowledge in this respect is important. If no hydro- 
chloric acid at all is secreted, the stomach can be regarded only as 
a storehouse, as it were, and proteids must be ordered in such form 
that they may be subjected to the process of pancreatic digestion 
with as little delay as possible, the nutrition of the body being 
aided, if necessary, by a suitable administration of predigested food. 
If, on the other hand, an amount of hydrochloric acid is secreted 
sufficient to saturate the albuminous affinities of an ordinary meal, 
or at least of moderate amounts of proteids, the dietetic directions 
need not be so stringent. While in the former case the absence of 
loosely combined hydrochloric acid usually indicates complete de- 
struction of the glandular elements of the stomach — in other words, 
an irreparable condition — a fair prognosis may be given when the 
amount of acid secreted is sufficient for the saturation of the albu- 
minous affinities of an ordinary meal. The following table 1 shows 
the amount of HC1 necessary to saturate the affinities of known 
amounts of various articles of diet, the figures given referring to 
100 c.c. or 100 grammes : 

1 Taken from Ehrlich : Dissert. Erlangen, 1893. 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 



1 35 



Milk . 






( ►. ^i-'-u. -1*J gramme 


Beef (boiled) 






. 2.0 grammes 


Mutton boiled) . 






. L.9 


Veal (boiled) 






. 2.2 " 


Pork (boiled) 






. 1.6 


Sweetbread (boiled) 






0.9 gramme 


( lalves 1 brain (boiled) 






. 0.G5 


Ham raw) 






1.9 grammes 


Ham (boiled) 






. 1.8 


Liver sausage 






. 0.8 gramme 


Cervelat sausage 






1.1 grammes 


Mettwurst . 






1.0 gramme 


Blood sausage 






. 0.3 


(I rab a in bread 






. 0.3 


Pumpernickel 






. 0.7 


Wheat bread 






. 0.3 " 


Rye bread . 






. 0.5 


Swiss cheese 






2.6 grammes 


Fromage de Brie 






. 1.3 


Edam cheese 






. 1.4 


Roquefort cheese 






. 2.1 


Beer (German) . 






0.07-0.15 gramme 



of pure 1 1' 1. 



The Quantitative Estimation of the Hydrochloric Acid of the 

Gastric Juice. 

Topfer's Method. The free and combined HC1 is most conve- 
niently estimated according to Topfer's method, which is both 
simple and sufficiently accurate for clinical purposes. 

In this method the total acidity (a) of a given amount of gastric 
juice — i. e., the acidity referable to the presence of free HC1, 
combined HC1, acid salts, and any organic acids that may be 
present — is first determined (lactic acid and the fatty acids, if 
present, need not be removed), using phenolphthalein as an 
indicator. This is followed by a determination of the acidity 
referable to free acids and acid salts in the same amount of gastric 
juice (b), using alizarin (alizarin monosulphonate of sodium) as an 
indicator. As this does not react with loosely combined HC1, the 



latter. The free HC1 (c) is finally estimated with dimethyl-amido- 
azo-benzol as an indicator, the difference between a and b + c giving 
the acidity referable to organic acids and acid salts. 

The solutions required are the following: 

1. A decinormal solution of NaOH. 



136 CLINICAL DIAGNOSIS. 

2. A 1 per cent, alcoholic solution of phenolphthalein. 

3. A 1 per cent, aqueous solution of alizarin. 

4. An 0.5 per cent, alcoholic solution of dimethyl-amido-azo- 
benzol. 

Three separate portions of 5 or lOc.c. of filtered gastric juice are 
measured off into three small beakers or porcelain dishes. To the 
first portion one or two drops of phenolphthalein are added, when 
it is titrated with the one-tenth normal solution of NaOH. It is 
necessary, however, to titrate to the point of a deep red, and not to 
the rose hue which first appears. It will be seen that upon the addi- 
tion of the first few drops of the one-tenth normal solution of NaOH 
the red color, which first appears, disappears on shaking. Upon fur- 
ther addition a point is finally reached when this no longer occurs, 
and the color of the entire solution suddenly turns to a rose. This 
rose color, however, is not the end-reaction that is to be obtained. 
If the titration is continued, it will be observed that a dark-red 
cloud forms in the light rose-colored solution, which disappears on 
shaking; finally a point is reached when an additional drop no 
longer intensifies the color of the solution. This point is the end- 
reaction which must be reached. 

To the second portion three or four drops of the alizarin solution 
are added, when it also is titrated with a one-tenth normal solution 
until a pure violet color is obtained. As some little practice is re- 
quired in order to determine this point with accuracy, Topfer advises 
to make previously the following simple tests: 

1. To 5 c.c. of distilled water add 2 or 3 drops of alizarin solu- 
tion, when a yellow color will result. 

2. To 5 c.c. of a 1 per cent, solution of disodium phosphate add 
the same number of drops, when a red or slightly violet color will 
be obtained. 

3. Five c.c. of a 1 per cent, solution of sodium carbonate treated 
with 2 or 3 drops of the alizarin solution will strike a pure violet, 
this being the color to be reached in the titration. 

In the third portion of the gastric juice the free HC1 is titrated, 
after the addition of 3 or 4 drops of the dimethyl-amido-azo-benzol, 
until the last trace of red — in the presence of free HC1 — has disap- 
peared. A yellow color resulting upon the addition of the indicator 
demonstrates the absence of free HC1, as has been shown on page 
131. The results are then calculated as shown in the following 
example : 



THE GASTRIC JUICE AND GASTRIC CONTENTS. ] 37 

Ten c.c. of gastric juice, using phenolphthalein as an indicator, 
required 10 c.c. of the one-tenth normal solution in order to bring 
about the end-reaction, while a like amount titrated in the same 
manner with alizarin required 7 c.c. in order to bring about the 
same result. The difference between 10 and 7 — i. e., 3 — would 
thus indicate the number of c.c. necessary to neutralize completely 
the amount of hydrochloric acid in combination with albuminous 
material. As 1 c.c. of the one-tenth normal solution represents 
0.00365 gramme of HC1, the amount of the acid thus held will be 
equivalent to 0.00365 X 3 = 0.01095 gramme of HC1; i. e. , 0.1095 
per cent. 

In the estimation of the free HC1 3.2 c.c. of the one-tenth normal 
solution were required, using dimethyl-am ido-azo-benzol as an indi- 
cator, corresponding to 0.00365 X 3.2; i. e., 0.1168 per cent., of 
HC1. The value of the total acidity in terms of HC1 is 10 X 
0.00365 = 0.0365 gramme for every 10 c.c. of gastric juice, or 
0.365 per cent. 

By deducting the amount of the free and combined HC1, viz., 
0.1095 -f 0.1168 = 0.2263, from this, it is found that the acidity 
of the gastric juice referable to organic acids and acid salts amounts 
to 0.1387 per cent., so that the results can be tabulated as follows: 

Free HC1 0.1168 per cent. 

Combined HC1 0.1095 

Organic acids and acid salts .... 0.1387 *' 



Total acidity .... 0.3650 per cent. 

The Method of Martius and Luttke (modified). This method 
is equally exact, but requires a greater expenditure of time. 

It is based upon the fact that upon incineration of the gastric 
juice the free HCl and that loosely combined with albuminous 
material escape, while the chlorine in combination with inorganic 
bases remains in the mineral ash, unless a very intense heat is applied 
for some time. By subtracting the amount of chlorine present in the 
latter form from the total amount, the quantity in combination with 
albuminous material and that occurring as free acid will be found. 
The total acidity of the gastric juice is then determined, and that re- 
ferable to the presence of the free and combined HCl subtracted 
therefrom, the difference giving the amount of organic acids present. 
By determining the acidity due to the presence of free HCl according 
to Topfer's method, and deducting the amount found from that 



138 CLINICAL DIAGNOSIS. 

referable to the presence of free and combined HC1, the amount of 
the latter is obtained. 
Reagents required: 

1. A solution of nitrate of silver in nitric acid of such a strength 
that 1 c.c. shall represent 0.00365 gramme of HC1. 

2. Liquor ferri sulphur, oxydati. 

3. A decinormal solution of ammonium sulphocyanide. 

4. A one-tenth normal solution of XaOH. 

5. A 1 per cent, alcoholic solution of phenolphthalein. 

6. A 0.5 per cent, alcoholic solution of dimethyl-amido-azo- 
benzol. 

Preparation of the solutions: 

1. The silver nitrate solution: As a solution is required of 
such a strength that 1 c.c. shall be equivalent to 0.00365 gramme 
of HC1, the amount of silver nitrate that must be dissolved in 
1000 c.c. of water is ascertained in the following manner : Since 
169.66 (molecular weight of AgN0 3 ) parts by weight of AgX0 3 
combine with 36.5 parts of HC1 (molecular weight of HC1), 
the amount of AgX0 3 required for each c.c. is found from the 
equation : 

169.66:36.5: :x: 0.00365; 36.5 x = 0.6192590; x = 0.0169. 

In one c.c. of the silver nitrate solution 0.0169 gramme of AgX0 3 
must thus be present, or 16.9 grammes in the litre. This quantity, 
or roughly 17 grammes, is weighed off and dissolved in 900 c.c. of 
a 25 per cent, solution of nitric acid, as the acid must be present in 
excess, the solution being purposely made too strong. To this solu- 
tion 50 c.c. of the liquor ferri sulphurati oxydati are added. The 
solution is then brought to the proper strength by titrating a known 
number of c.c. of a one-tenth normal solution of HC1 with the same, 
and correcting as usual. 

2. The ammonium sulphocyanide solution: A normal solution 
of ammonium sulphocyanide contains 75.98 grammes (molecular 
weight) per litre, and a decinormal solution 7.598 grammes. This 
quantity, or roughly 8 grammes, is dissolved in about 900 c.c. of 
water and the solution brought to the proper strength by titrating a 
known number of c.c. of the AgX0 3 solution with it, when every 
c.c. should correspond to 1 c.c. of the AgX0 3 solution; i.e., to 
0.00365 gramme of HC1. It is corrected as described elsewhere. 



THE GASTRIC JUICE AND GASTRIC CONTENTS. \:\<) 

Method: 

1. To determine the total amount of CI present: 10 c.c. of filtered 
gastric juice — Martins and Liittke make use of the unfiltered gas- 
tric contents — are measured off into a small flask bearing a 100 c.c. 
mark, and treated with an excess of the. one-tenth normal solution 
of AgNO s . Experience has shown that 20 c.c. are sufficient. The 
mixture is agitated and allowed to stand for ten minutes. Distilled 
water is then added to the 100 c.c. mark, the mixture agitated once 
more and filtered through a dry filter into a dry beaker. Fifty c.c. 
of the filtrate are titrated with the one-tenth normal solution of 
ammonium sulphocyanide until the blood-red color which appears 
upon the addition of every drop — due to the formation of ferric 
sulphocyanide — no longer disappears on stirring. By multiplying 
the number of c.c. of the ammonium sulphocyanide solution used 
by 2 (the number of c.c. that would have been necessary for the 
precipitation of the excess of silver in 100 c.c.) and deducting the 
result from the number of c.c. of the one-tenth normal solution of 
AgX0 3 employed, viz., 20, the number of c.c. of the latter solution 
is found which was necessary to precipitate the chlorine contained 
in 10 c.c. of the gastric juice. As 1 c.c. of the solution represents 
0.00365 gramme of HC1, it is only necessary to multiply this figure 
by the number of c.c. used in the precipitation of the chlorine. The 
resulting value, u T," expresses the total amount of chlorine 
present. 

As a general rule, it is not necessary to decolorize the gastric 
juice. If required, however, 5 to 15 drops of a 5 per cent, solution 
of potassium permanganate may be added to the 10 c.c. employed, 
after the mixture has stood for ten minutes. 

2. Determination of the amount of CI in combination with inor- 
ganic bases, " F." Ten c.c. of the filtered gastric juice are care- 
fully evaporated to dryness in a platinum crucible over a water- 
bath or upon a plate of asbestos, in order to avoid sputtering (as 
the heat applied in the process of incineration is not very intense, 
a porcelain crucible may also be employed). The residue is then 
carefully incinerated over the open flame, the process being only 
carried to the point when the organic ash no longer burns with a 
luminous flame. Intense heat should be avoided, as the chlorides 
are volatilized upon the application of red heat. On cooling the 
ash is moistened with a few drops of distilled water and mixed with 
a stirring-rod, when the residue is extracted in separate portions with 



140 CLINICAL DIAGNOSIS. 

100 c.c. of hot, distilled water and filtered. This amount is usually 
sufficient to dissolve out the chlorides present. If any doubt should 
exist, however, it is only necessary to add a drop of AgN0 3 solution 
to a few drops of the last portion of the filtrate : the formation of a 
cloud, referable to silver chloride, will necessitate still further wash- 
ing. The whole filtrate is then treated with 10 c.c. of the one-tenth 
normal solution of Ag]TO 3 , and the amount of AgN0 3 consumed in 
the precipitation of the chlorides determined by titration with the 
one-tenth normal solution of ammonium sulphocyanide, as described 
above. The HC1 present in combination with inorganic bases is 
thus determined. The difference between the amount of HC1 present 
in combination with inorganic bases and the total amount of chlorine 
in terms of HC1 will then indicate the amounts of the free and of the 
combined HC1 present, termed " L" and " C," respectively; hence 
T — F = L + C. 

3. The total acidity in terms of HC1 is further determined accord- 
ing to the method given elsewhere (see p. 122) and indicated by the 
letter u A." The difference between the total acidity and the 
amount of free and combined HC1 will represent the amount of 
organic acids and acid salts, " O " ; hence O = A — (L + C). 

The free HC1 finally is determined according to the method 
of Topfer. The difference between the value thus found and that 
expressing the amount of free and combined HC1 will indicate the 
amount of the latter; hence (L -f- C) — L = C. 

Leo's Method. This method is based upon the observation that 
calcium carbonate combines with free and combined HC1 at ordinary 
temperatures to form neutral calcium chloride, while the acid phos- 
phates are not affected. It is thus clear that by determining the 
total acidity of the gastric juice, and deducting from this the acidity 
referable to acid salts, the amount of the physiologically active HC1 
— i. e., of free and combined HC1 — is obtained. 

As it has been shown that in the presence of CaCl 2 (formed, as 
indicated above, upon the addition of CaC0 3 ), owing to the forma- 
tion of calcium monophosphate — CaHP0 4 , twice the quantity of 
NaOH is taken up by the same quantity of the diacid salt, it is 
necessary to titrate after the addition of an excess of CaCl 2 . 

Reagents required: 

1. A one-tenth normal solution of NaOH. 

2. A 1 per cent, alcoholic solution of phenolphthalein. 

3. A concentrated solution of CaCl 2 . 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 141 

4. Chemically pure CaCO s . The purity of the salt may be tested 

by stirring a small piece with water; the solution should not color 
red litmus-paper blue. A solution of the salt in dilute HC1 should 
not yield a precipitate when treated with sulphuric acid. 

Method: Organic acids that may be present are first removed by 
shaking with ether, 50 to 100 c.c. of this being required for every 
10 c.c. of gastric juice. The total acidity of the gastric juice is then 
determined in 10 c.c. of the filtered liquid after the addition of 5 
e.e. of the concentrated solution of calcium chloride, the result being 
termed "A." 

The acidity referable to the presence of acid phosphates is deter- 
mined as follows: 15 c.c. of filtered gastric juice are treated with a 
pinch of dry and chemically pure calcium carbonate; the mixture 
is thoroughly stirred, and passed at once through a dry filter. Ten 
c.c. of the filtrate, from which the C0 2 formed is expelled by means 
of a current of air, are then treated with 5 c.c. of the calcium chlo- 
ride solution and titrated as above, the resulting value being termed 
" P. " A — P is, hence, equivalent to L + C. The value of " C ' ' 
can then be ascertained by determining the acidity referable to free 
HC1 according to Topfer's method, and deducting the value found 
from L + C. 

This method is sufficiently accurate for practical purposes, and 
has the additional advantage of not requiring the expenditure of 
much time. 



The Ferments of the Gastric Juice and their Zymogens. 

Pepsin and Pepsinogen. According to our present views, the 
zymogen of pepsin, viz., pepsinogen or propepsin, and not pepsin 
itself, is secreted by the chief cells of the fundus glands. This 
view is based upon the observation that an aqueous extract of the 
mucous membrane of the stomach of a fasting animal recently killed 
does not lose its digestive power when treated with a 1 per cent, 
solution of sodium carbonate at a temperature of from 38° to 40° C. 
for a considerable length of time, whereas pepsin itself is rapidly 
destroyed by very dilute solutions of the alkaline carbonates. It 
is thus natural to conclude that the glands of the stomach do not 
contain pepsin, but some other substance during the process of fast- 
ing which is capable of resisting the action of sodium carbonate, and 
which can be transformed into pepsin by the addition of HC1. This 



142 CLINICAL DIAGNOSIS. 

substance has been termed pepsinogen or propepsin. As a rule, 
pepsin is only obtained from the mucous membrane of the digesting 
organ, while at other times the physiologically inactive zymogen is 
found. As the zymogen, moreover, is probably always present 
together with pepsin in the gastric juice obtained from healthy in- 
dividuals during the process of digestion, it is not clear whether 
the transformation of the zymogen into its ferment takes place in 
the body of the cell or after secretion. The greater part of the 
evidence so far is in favor of the latter view. 

This is not the place to enter into a detailed consideration of the 
various properties of pepsin, and it will suffice to say that the 
activity of the ferment is destroyed by even very dilute solutions 
of the alkaline carbonates. The same result is reached by exposing 
a watery solution of pepsin to a temperature of 70° C, while in its 
dry state a temperature of 100° C. will not destroy its activity, as 
is shown by the fact that a specimen of pepsin thus treated is, on 
cooling, still capable of digesting albumins in the presence of HO. 

While pepsin is capable of digesting albumins in the presence of 
other acids, viz., phosphoric, sulphuric, oxalic, acetic, lactic, and 
salicylic acid, the solutions must be stronger than in the case of 
HC1. TTith lactic acid, for example, a satisfactory result is only 
reached with a concentration of from 12 to 18 p. m., while of HO 
2 to 4 p. m. are sufficient. Larger or smaller amounts do not act so 
promptly. 

Very important from a practical standpoint is the fact that but 
small quantities of pepsin are required to digest large amounts of 
albumin, and Petit, for example, claims that a pepsin preparation 
from his own laboratory was capable of dissolving 500,000 times 
its weight of fibrin in seven hours. This property on the part of 
pepsin of doing an amount of work that is entirely out of proportion 
to the amount of ferment present is common to all ferments, and is 
dependent upon the fact that the ferment itself undergoes no change 
during the process. 

Exact figures expressing the quantity of pepsin or of its zymogen 
produced in the twenty-four hours are lacking, and inferences can 
hence only be drawn as to the physiologic activity of the ferment 
from the rapidity with which given amounts of albuminous mate- 
rial are digested. This, however, depends to a large extent upon 
the nature and the concentration of the free acid present. In physio- 
logic conditions 25 c.c. of gastric juice will dissolve 0.05 to 0.06 



THE GASTRIC JUICE AND QASTMIC CONTENTS. H;3 

gramme of serum-albumin in one hour, the same amount of coagu- 
lated egg-albumin in three hours, and a like amount of fibrin in one 
hour and a half. 

As abnormalities in the circulation and innervation of the stomach 
do not apparently influence the production of pepsin, or rather of its 
zymogen, a diminution in the degree of peptic activity, or its total 
absence, may be referred directly to disease of the stomach itself, 
viz., its glandular apparatus. The determination of the presence 
or absence and relative amount of pepsin in the gastric juice, hence, 
actually furnishes us with more directly useful information than the 
recognition of the presence or absence of free HC1, as the secretion 
of the latter is influenced by many factors which, as has been shown, 
only indirectly affect the process of digestion. 

As pepsin is formed from pepsinogen through the agency of a 
free acid, notably of HC1, its presence, in the absence of organic 
acids, in notable quantities at once indicates the presence of hydro- 
chloric acid. It may be said, vice versa, that if free HC1 be present 
in the gastric juice, and the latter digest albumins, pepsin also will 
be found. Should the zymogen alone be present digestion will take 
place only upon the addition of an acid, while an entire absence of 
digestion upon the addition of HC1 will indicate the absence of 
both pepsin and its zymogen. At times, though rarely, a u gastric 
juice " is met with which is capable of digesting albumin in the 
absence of HC1, owing to the presence of pancreatic juice — a point 
which may be of great value, both from a diagnostic and a prog- 
nostic point of view. 

In the differential diagnosis of a chronic gastritis and a neurosis, 
or a dyspeptic condition referable to hyperemia of the gastric mucous 
membrane, the demonstration of the presence of the zymogen in the 
absence of HC1 may, at times, be very important, bearing in mind 
the fact that circulatory and nervous disturbances do not apparently 
influence the production of pepsinogen. An entire absence of the 
latter would, of course, warrant the diagnosis of complete anadeny 
of the stomach. 

Tests for Pepsin and Pepsinogen. Test for the enzyme : If 
the presence of free HC1 has been previously ascertained, 25 c.c. 
of filtered gastric juice are set aside and kept at a temperature of 
from 37° to 40° C, a bit of coagulated egg-albumin, fibrin, or 
serum-albumin being added. In order to permit of a comparison 
of results the same amounts should always be taken; 0.05 to 0.06 



144 ciiyiCAL l:a :-:■: sjs 

gramme of egg-albumin, as has been shown, ought, under physio- 
logic conditions, to be digested after three hours. 

Test for the zymogen - Should HC1 be absent the test is made in 
: he same manner after the addition of from : to : drops ;f the 
officinal solution of HC1 to i" of the nitrate. Under such 

conditions — i. e. y in the absence of free HO — pepsinogen alon- is 
found as a rule. 

Quantitative estimation of pepsin. Accurate methods for the quan- 
tita:i" r esti ination of pepsin, as such, do not exist, and relative 
values only can be obtained. Most convenient is the method sug- 
gested by Hammerschlag: Three Esbach's tubes (albuniininieters) 
are emplc fed. Tube A is tilled to the mark U with a mixture of 
10 cc. of a 1 per centw solution of seruni-albuniin in 0.4 per cent, 
of hydrochloric acid, aud 5 cc. of iltered gastric juice. The second 
tube, B. which is the standard, is likewise filled to the mark U, but 

; gramme of pepsin is added to the serum solution, instead of 
the gastric juice. Tne third tube. C, merely contains a mixture of 
the serum solution and 5 : . of water. After having been kept in 
one hour at a temperature of 37° C, Esbach's 
ed to each tube to the mark E. After standing 
irs the amount of precipitated albumin is read 
the difference between that in A and C compared with 



"D 



Estimation of pepsinogen. In order to estimate the amount of 
pepsinogen the method of Boas may be conveniently employed. 
T :• this end the gastric juice is diluted with distilled water in vary- 
ing proportions, such as 1 . 1 : 10, 1 : 20, etc. A known quantity 
of coagulated albumin is added to each specimen, as also one or two 
drops of an officinal solution of HC1 for every 10 c.c. employed. 
These tubes are kept at a temperature of from 37° to 10° C, and 
the degree of dilution noted at which the bit of egg-albumin con- 
tinues to be dissolved. The greater the degree of dilution at which 
dige-:: still takes place, the greater the amount of pepsin or of 
its zymogen present. 

If it is si] to definitely exclude the presence of pepsin and 

pepsinogen in the stomach, the method of Jaworski should be 

employed. To this end about 200 cc. of a decinormal solution of 

hydrochloric acid are poured into the stomach through a tube and 

rated after one-half hour. If the fluid removed contains no 

:he absence of both enzyme and zym gen may be inferred. 



THE GASTRIC .inch' AND GASTRIC CONTENTS. 145 

The Milk-curdling Ferment and its Zymogen, viz., Chy- 
me-sin and Chymosinog-en. A great deal of what 1ms been said 
above regarding pepsin and its zymogen also holds good for chy- 
mosin and its proenzyme. The proenzyme thus also appears to be 

formed by the cell, as a neutral aqueous extract of the mucous mem- 
brane of the stomach does not, as a rule, contain the ferment, but 
the zymogen, the former only resulting when the latter is treated 
with a free aeid. It differs from pepsin in that it can exert its 
physiologic activity in feebly acid, neutral, and even feebly alkaline 
solutions. Exposure of an active solution of chymosin containing 
3 p. m. of free HC1, moreover, to a temperature of from 37° to 
40° C, leads to its destruction, while pepsin is not affected under 
the same conditions. 

Its specific action is exerted upon milk or lime-containing solu- 
tions of casein, leading to a coagulation of the latter in neutral or 
feebly alkaline solutions. 

In this connection it is important to note that the addition of a few 
c.c. of a solution of calcium chloride, or any other soluble lime salt, 
resnlts in a transformation of the zymogen into the physiologically 
active ferment, and that HC1, while it normally causes such trans- 
formation, is not absolutely necessary in the presence of calcium 
chloride. 

Under physiologic conditions chymosin and its zymogen are 
always present in the gastric juice. In disease the inferences that 
can be drawn from a quantitative estimation of the ferment and its 
zymogen have been well formulated by Boas, to whom we are 
especially indebted for a great deal of valuable information in this 
connection: 

1. Not withstanding the absence of free HC1, chymosin may still 
be present, although in minimal traces; i. e., demonstrable with a 
dilution of from 1 : 10 to 1 : 20 (see method given on p. 146). 

2. In the absence of free HC1 the zymogen may still be preseut 
in normal amounts — i. e., with a dilution of from 1 : 100 to 1 : 150. 
The presence of the zymogen, especially when repeatedly observed, 
permits of the conclusion with a high degree of probability, and 
even with absolute certainty, that we are not dealing with an organic 
disease of the stomach, but with a neurosis, or a hypersemic condi- 
tion of the mucous membrane referable to disease of other organ-. 

3. The zymogen may occur in moderately diminished amount, 50 
per cent, only being present. This is usually owing to the exist- 

10 



146 CLINICAL DIAGNOSIS. 

ence of a gastritis which has not as yet reached its highest degree 
of severity. The nearer the amount of zymogen approaches to 
normal, the greater will be the probability of an ultimate recovery 
under suitable treatment. 

4. The amount of the zymogen is greatly diminished (dilations 
of 1 : 10 to 1 : 25 yielding a negative result), or may be absent alto- 
gether. In cases of this kind a severe and usually incurable gas- 
tritis exists, either primary or occurring secondarily to carcinoma, 
amyloid degeneration, etc. 

5. In 1, 2, and 3 the re-establishment of the secretion of HC1 
may be attempted with some prospect of success by means of stimu- 
lating remedies. 

These conclusions are based upon the employment of Ewald's 
test-breakfast, and cannot be applied to observations made after 
other test-meals, without previous studies in this direction. 

Testing for the presence of chymosin and its zymogen, moreover, 
is of decided value in cases in which alkaline material is vomited, 
and where we may be called upon to decide whether this contains 
constituents of the gastric juice or not. 

Tests for Chymosin and Chymosinog-en. Test for the enzyme; 
Five to ten c.c. of milk are treated with from three to five drops of 
the filtered gastric juice and kept at a temperature of from 37° to 
40° C. for ten to fifteen minutes. If coagulation occurs during 
this time, it may be definitely concluded that the enzyme is present. 

Test for the zyomgen : 10 c.c. of filtered and feebly alkaline gastric 
juice are treated with 2 or 3 c.c. of a 1 per cent, solution of calcium 
chloride, aud kept at a temperature of from 37° to 40° C, when 
the formation of a thick cake of casein will be observed within a 
few minutes in the presence of the zymogen. 

Quantitative Estimation. Of the enzyme : This is based upon 
the fact that upon gradually diluting a specimen of gastric juice a 
point is finally reached at which a chymosin reaction can no longer 
be obtained, the value being, of course, a relative one. Under 
physiologic conditions a positive reaction can still be obtained with 
a degree of dilution varying between 1 : 30 and 1 : 40. 

The gastric juice is neutralized with a very dilute solution of 
sodium hydrate and tubes prepared containing from 5 to 10 c.c. of 
the gastric juice, variously diluted in the proportion of 1 : 10, 1 : 20, 
1 : 30, etc., to which an equal amount of neutral or amphoteric milk 
is added. The tubes, properly labelled, are kept at a temperature 



THE GASTRIC JUICE AND QASTRIC CONTENTS, 147 

of from 37° to 40° C, and the degree of dilution noted at which 
coagulation still occurs. 

Of the zymogen : The gastric juice is rendered feebly alkaline and 
tubes arc prepared containing equal amounts of milk and gastric 
juice, the latter variously diluted as above directed; the examination 
is then carried on in the same manner. Normally a positive reaction 
is obtained with a dilution varying between 1 : 100 and 1 : 150. 
Allowance must, of course, be made for the error incurred in 
diluting the gastric juice during the process of neutralization. 

The Products of Gastric Digestion. 

The Digestion of Native Albumins. The first step in the 
process of albuminous digestion in the stomach is one of swelling, 
which may be readily observed when a flake of fibrin, for example, 
is placed in gastric juice, and the temperature of the latter main- 
tained between 37° and 40° C. Very soon simple dissolution 
takes place, which is followed by the process of " denaturization," 
as Xeumeister terms it, in which the native albumins are trans- 
formed into acid albumins or syntonins, owing to the continued 
activity of the HC1 and pepsin. The pepsin, however, only acts 
as an adjuvant to the acid, and HC1 alone is capable of effecting 
the same result. While in the absence of pepsin more concentrated 
solutions of the acid and a higher temperature are required, the 
temperature of the body and the amount of HC1 secreted by the 
stomach are sufficient when pepsin is present. The latter, in the 
absence of free HC1, is perfectly inert. 

The " denaturization " of the native albumins is followed by a 
splitting up of the albuminous molecule and a process of hydration, 
the so-called primary albumoses, of which there are two, viz., 
protoalbumose and heteroalbumose, being the first products thus 
formed. 

Dysalbumose, it may be stated in passing, is merely a modified 
form of heteroalbumose, which results from the latter when this is 
dried or kept under water for some time. 

During the further process of digestion a deuteroalbumose results 
from each of the primary albumoses, and from these finally peptones, 
to which, in contradistinction to the peptones formed during the 
process of pancreatic digestion, the term " amphopeptonc " has 
been applied by Kuhne. 



148 CLINICAL DIAGNOSIS. 

The relation existing between the various products of gastric 
digestion may be seen from the table below (taken from Xeumeister) : 

Native albumin. 



Protoalbumose. Heteroalbumose (dvsalbumose). 

I I 

Deuteroalbumose. Deuteroalbumose. 

I I 

Peptone (amphopeptone) Peptone (amphopeptone). 

The transformation of native albumins into peptones, as described, 
was first worked out for fibrin, but was subsequently shown to hold 
good for all native albumins of both vegetable and animal origin. 
Chittenden proposes the generic term " proteoses " for these various 
products of digestion, in contradistinction to those resulting from 
albuminoids. Vitellin thus first yields two primary vitelloses, viz., 
a proto- aDd a heterovitellose, which are transformed into deutero- 
vitelloses and finally into peptones. The albumoses of fibrin are 
similarly termed fibrinoses; those of the globulins, globulinoses; 
and those of myosin, myosinoses. 

The digestion of casein, which belongs to the class of nucleoalbu- 
mins, differs from the process described. The casein of the milk is 
present in solution as a neutral calcium salt, and as casein has the 
character of a polybasic acid, CaCl 2 , and the corresponding acid 
casein salt will result in the presence of the HC1 of the stomach; 
still later, when more HC1 has been secreted, insoluble casein as 
such will be found. While HC1 is thus capable of causing the 
precipitation of casein, it has also been shown that the same result 
may be reached in the absence of HC1, and, according to Hammar- 
sten, is brought about in consequence of a hydrolytic action on the 
part of the chymosin present, the Ca salt of paracasein (cheese) and 
a small amount of albumose-like posset-albumin being formed. 
This latter process is now supposed to take place in the stomach 
after the HC1 has previously transformed the neutral into the acid 
casein salt. When this stage is reached the paracasein is split up 
into an albumin and an insoluble nuclein, owing to the action of 
HC1 and pepsin. The albumin is then further digested as described, 
two primary caseoses first resulting, which are then transformed 
into deutero-caseoses, and these finally into peptones. 

The remaining proteids, such as haemoglobin, glucosides, etc. , are 
similarly acted upon by the gastric juice, being first split up into 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 149 

the corresponding albumins and their pairlings. Haemoglobin is 

thus broken down into luematin and an albumin, which latter 
undergoes the same process of digestion as seeu in the case of the 
native albumins. 

The Digestion of the Albuminoids. Of the albuminoid bodies 
onlv collagen and elastin undergo digestion in the stomach, eelatoses 
and elastoses being formed during the process, while keratin passes 
off undigested. Heteroproteoses, however, are formed from neither 
collagen nor elastin, but merely protoproteoses, which in turn are 
transformed into deuteroproteoses, of which there is only one kind, 
viz., that corresponding to the protoproteose, peptone finally result- 
ing. 

The Digestion of Carbohydrates. The secretion of the stomach 
itself is not capable of digesting carbohydrates. There appears to 
be no doubt, however, that a transformation of starches into sugar 
takes place during the earlier stages of digestion. This is owing 
to the continued action of the pytalin of the saliva (see p. 102) in the 
stomach, which goes on until the amount of HC1 secreted reaches 
0.01 or more per cent., it being remembered that the transformation 
of starches into sugar goes on best in a neutral or feebly alkaline 
medium. 

The question whether or not a diastatic ferment occurs in the 
mucus secreted by the stomach itself is unimportant, as cases have 
but rarely been observed in which there was an absence of ptyalin 
from the saliva. 

As indicated in the chapter on Saliva, a large number of inter- 
mediary products are formed in the transformation of starch into 
sugar, of which an idea may be had from the accompanying table: 

Starch. 

I 

Amidulin. 

I 

I ~~ " 1 

Erythrodextrin. Maltose. 

I I 

Achroodextrin a Maltose. 

Achroodextrin /3 Maltose. 

I I 

Achroodextrin 7 (maltodextrin). Maltose. 

Maltose. Maltose. 

In the mouth this transformation is very rapidly effected in the 
case of certain starches, such as corn-starch and rye-starch, and it is 



1 50 CL IXICA L DIA GXO SIS, 

possible to demonstrate the presence of sugar after from two to six 
minutes. Potato-starch, on the other hand, requires a much longer 
time. viz.. from two to four hours. This difference is entirely de- 
pendent upon the varving degrees of resistance offered to the action 
of the saliva bv the enclosing envelope of cellulose, as is apparent 
from the fact that a paste made from potatoes is just as rapidly 
digested as one made from rye. 

For practical purposes, the digestion of carbohydrates in the 
stomach may be disregarded as insignificant. 

Fats are not Digested, at oil in the Stomach. 

From the above considerations it is apparent that under physio- 
logic conditions a mixture of these various products is met with in 
the stomach at the height of digestion, and it might be expected 
that from a preponderance of one over the other definite and valu- 
able conclusions as to the digestive power of the organ could be 
reached. While this is true in a certain sense, the quantitative 
methods of analysis that would have to be employed in order to 
obtain definite data are as yet too complicated for the purposes of 
the clinician, and from the simple qualitative tests not much infor- 
mation can be derived. The recognition of the presence of peptones 
would thus merely indicate the presence of HC1 and pepsin in a 
general way. as peptones may be formed in the absence of HO and 
in the presence of organic acids, which may be found in pathologic 
conditions. Moreover, a portion of the albumin of milk. egg-. 
meat, etc., is already peptonized, so to speak, during the process of 
boiling. It is not surprising that peptones may probably be demon- 
strated in every specimen of gastric contents. 

A large amount of syntonin and primary albumoses in the pres- 
ence of a feeble peptone-reaction must, of course, be regarded as 
abnormal, pointing to a defective secretion of either HO or enzymes, 
or of both. The same may be said to hold good when a pronounced 
peptone-reaction disappears upon the removal of syntonin and the 
primary albumoses. 

As far as the examination for the products of carbohydrate diges- 
tion is concerned, it may be stated, as a general rule, that in the 
presence of a normal amount of HO erythrodextrin can usually be 
demonstrated near the end of gastric digestion, whilj achrobdextrin 
is almost alwavs obtained at the same time in the absence of free 



THE GASTRIC JUICE AND i.ASTRIC CONTENTS. 151 

HC1, so that the tests for the presence of these two bodies may be 
regarded as roughly indicating the presence or absence of free 1 1 ( 1 , 
and as therefore yielding the same information as the tests for this. 
Boas draws attention to the fact, however, that ptyalin may, at 
times, though rarely, be absent, when conclusions drawn from these 
tests as to the presence of HC1 would be erroneous. 

The tests for sugar in the gastric juice do not furnish any infor- 
mation that is of practical value. 

Analysis of the Products of Albuminous Digestion. 

In order to separate the various bodies referred to from each 
other the following procedure is employed : 

The filtered gastric contents are carefully neutralized with a dilute 
solution of XaOH, using litmus-paper to determine the reaction, a 
small drop of the mixture being placed upon the paper from time 
to time during the addition of the XaOH, until no change in color 
is produced either on the red or the blue paper. If syntonin be 
present, it will be precipitated, and can be collected on a small filter. 
Upon the addition of an excess of dilute acid or an alkali this pre- 
cipitate will again be dissolved. The filtrate is feebly acidified by 
the addition of a few drops of a very dilute solution of acetic acid, 
treated with an equal volume of a saturated solution of common 
salt, and brought to the boiling-point. Any native albumin that 
may be present in solution is thus coagulated and can be filtered off 
on cooling. In the filtrate the albumoses and peptones remain. 
The presence of the former may be demonstrated by adding a few 
drops of HX0 3 to a specimen, when a precipitate will form which 
dissolves upon the application of heat, to reappear on cooling; if 
necessary, the specimen may be diluted. 

Should the deuteroalbumoses of vitellin or myosin be present, 
this test yields a negative result, and a precipitate only occurs when 
the solution, acidified with nitric or acetic acid, is completely satu- 
rated with XaCl. 

The presence of primary albumoses, on the other hand, may be 
established by adding pieces of rock-salt to the neutral solution, 
when a precipitate occurs in their presence. The albumoses may 
be roughly separated from the peptones by saturating the acidified 
filtrate just obtained with pulverized ammonium sulphate, whereby 
the albumoses are almost entirely precipitated. A small portion of 



152 



CLINICAL DIAGNOSIS. 



the deuteroalbumoses, however, resulting from the protoalbomoses 
remains in solution and passes into the nitrate, which also contains 
all of the amphopeptone. In the nitrate these products may be 
demonstrated by adding a concentrated solution of NaOH, care 
being taken to keep the temperature from rising too high by immer- 
sion in cold water until all ammonium sulphate has been transformed 
into sodium sulphate and a slight excess of the NaOH is present. 
The sodium sulphate, which separates out during this process, is 
allowed to settle, and a 2 per cent, solution of sulphate of copper 
carefully added drop by drop to a specimen taken from the super- 
natant fluid. In the presence of peptones a rose to a purplish-red 
color will develop. 

The peptones may be obtained after careful neutralization of the 
filtrate, having first diluted this with an equal volume of distilled 
water, by the addition of a solution of tannic acid, care being taken 
to avoid an excess, as the peptone-precipitate is soluble under such 
conditions. 

From the following table an idea may be formed of the reactions 
of these various bodies : 

Reaction of the Individual Proteids. 





Globulin. 


Syntonin. 


Hemialbumose. 


Peptone. 


Soluble in 


Dilute solutions of 
sodium chloride 
and of magnesium 
sulphate. 


Dilute acids and 
alkalies. 


Water acids, alka- 
lies, and salts. 


Water, acids, acids 
+ salts, alkalies. 


Insoluble in 


Water. 


Water and neutral 
salt solutions. 






Precipitated by 


Much water, heat- 
ing to 75° C, satu- 
ration with mag- 
nesium sulphate 
from its solutions 
in neutral salts. 


Neutralization of its 
solutions in dilute 
acids, by means of 
sodium chloride or 
heating to 75° C. 
from acid solu- 
tions. 


Acetic acid+sodium 
chloride, concen- 
trated nitric acid, 
acetic acid, and 
potassium ferro- 
cyanide in the 
cold. 


Bichloride of mer- 
cury, tannic acid, 
iodo-mercuric io- 
dide of potassium, 
phospho-tungstic, 
and phospho-mo- 
lybdic acids. 


Biuret re- 
action 


Violet. 


Violet. 


Rose to purple. 


Rose to purple. 



Tests for the Products of Carbohydrate Digestion. 



Starch may be recognized by the fact that it strikes a blue color 
with a solution of iodo-potassic iodide, while the same solution gives 
a violet or mahogany-brown with erythrodextrin. To this end it 
is only necessary to add a drop or two of LugoPs solution to a few 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 153 

c.o. of the filtered gastric juice. The presence of achroodextrin may 
be inferred if no change in color is produced upon the addition of 
the reagent. 

Maltose and dextrose, which both react with Fehling's solution 
and undergo fermentation, differ from each other by the fact that 
the former does not reduce Barfoed's reagent, which is prepared by 
adding a 1 per cent, solution of acetic acid to a 0.5 to 4 per cent, 
solution of acetate of copper. Upon boiling a few c.c. of this solu- 
tion, and adding a small amount of gastric juice, red cuprous oxide 
will be precipitated in the presence of maltose. 

Lactic Acid. 

Mode of Formation and Clinical Significance. It was for- 
merly thought that the acidity of the gastric juice was referable to 
the presence of lactic acid, as this can always be demonstrated in 
the beginning, at least, of the process of digestion, and the HC1 was 
even thought to result from an action of the lactic acid upon the 
chlorides ingested. That this view was erroneous C. Schmidt suc- 
ceeded in demonstrating beyond a doubt, as has been shown on p. 
120. An explanation of the presence of lactic acid suggested itself 
when Miller found that normally various bacteria occur in the 
mouth capable of forming lactic acid from sugar, and that a number 
of bacteria can be isolated from the gastric contents which are capable 
of causing an acid fermentation in sugar-containing media. 

There would, hence, be nothing surprising in the constant occur- 
rence of lactic acid, as the two principal factors necessary for its 
formation are probably always present after the ingestion of an 
ordinary meal, viz., carbohydrates and bacteria capable of causing 
lactic-acid fermentation. The absence of the lactic acid during the 
later stages of digestion was, furthermore, explained by the fact 
that lactic-acid fermentation ceases in the presence of from 0.7 to 
1.6 pro mille of HC1; i. e., in the presence of the amount of HC1 
which is found in normal gastric juice. The occurrence of lactic- 
acid fermentation in the stomach was, hence, until quite recently 
regarded as an established fact. At this stage Martins and Liittke, 
employing the method already described, found " that the accurately 
determined curve of acidity referable to HC1 coincided in all re- 
spects, even at the beginning of the process of digestion, with the 
curve referable to the total acidity/ ' so that lactic acid as a physio- 



154 CLINICAL DIAGNOSIS. 

logic constituent could not have been present in the gastric contents 
examined. 

Recent researches of Boas, moreover, appear to prove beyond a 
doubt that in physiologic conditions no appreciable amounts of 
lactic acid are formed during the process of digestion, and that the 
lactic acid found after an ordinary meal has been introduced into 
the stomach as such. That lactic acid is actually present in the 
various kinds of bread has been definitely proved, and it is, hence, 
not permissible to make use of any test-meal containing lactic acid 
when the question as to its formation in the stomach is to be con- 
sidered. For these reasons Boas suggests the use of simple oatmeal- 
soup to which salt only has been added. For practical purposes 
this is probably not always necessary, as the amount of lactic acid 
found after Fwald's test-breakfast may be disregarded in health, 
and an increased amount be directly referred to pathologic condi- 
tions. 

The fact that the lactic acid disappears, or at least is no longer 
demonstrable, at the height of digestion, Boas refers to resorption 
or a carrying off of the acid introduced on the one hand, or to an 
interference of the HC1 with the delicacy of the reagent usually 
employed — i, e., Uffelmann's reagent — on the other. Pathologic- 
ally the same rule may be said to hold good, since Boas was unable 
to demonstrate its presence after the exhibition of his test-meal in 
various diseases of the stomach, viz., chronic gastritis, atony and 
dilatation referable to myasthenia, or pyloric stenosis following 
ulcer. Mere traces, which were occasionally observed, are of no 
significance, and possibly referable to lactic-acid fermentation hav- 
ing taken place in the mouth. In all of the cases examined, more- 
over, no organic acids could be demonstrated by the method of 
Hehner-Seemann (see p. 163). 

It is apparent then that notwithstanding stagnation of the gastric 
contents and the absence of free HC1 in normal amounts, lactic acid 
is not necessarily formed in the stomach, even in the presence of 
carbohydrates. In only one disease of the stomach was lactic acid 
found by Boas in notable quantities, viz., carcinoma. This observa- 
tion is in accord with the fact that Uffelmann's test here yields a 
marked reaction — i. e., a deep lemon or canary-yellow color — even 
upon the addition of but a few drops of the gastric juice, while in 
the benign affections only a pale-yellow, brownish, or grayish color 
is obtained. 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 155 

Boas' test-meal should be given the evening before the examina- 
tion, the stomach having* been previously washed free from all 
remnants of Unnl, and the remaining contents examined the next 
morning. 

In an analysis of fourteen cases of carcinoma Boas was able to 
demonstrate the presence of lactic acid in amounts varying between 
1.22 and 3.82 p. m. in all cases but one. In this connection it may 
be mentioned that under physiologic conditions the amount of lactic 
acid obtainable after Ewald's test-breakfast varies between 0.1 and 
0.3 p. m. 

That stagnation of the gastric contents and the absence of free 
HC1 alone are not capable of causing the formation of lactic acid 
has been seen, and it is, hence, difficult to explain why in carcinoma 
only lactic-acid fermentation should occur. Whether the malignant 
growth itself must be regarded as one of the principal factors in this 
connection, as Boas suggests, must still remain an open question. 

If the difficulties that may be encountered in the diagnosis of car- 
cinoma, and notably in the beginning of the disease, be remembered, 
Boas' observation must be regarded as of the greatest importance, 
for, if confirmed, we should actually be in possession ofa" specific " 
symptom of carcinoma of the stomach. The fact that lactic acid is 
present in the beginning of the disease makes Boas' observations 
still more important, as satisfactory results from operative inter- 
ference can only be expected during the earliest stages of the malady. 

Owing to the interest which attaches to this subject, it may not 
be out of place to refer briefly to the following observation of 
Koch: In a case in which ulcer of the stomach existed, associated 
with the presence of free HC1, suddenly a positive HC1 reaction 
could no longer be obtained, while lactic acid appeared and increased 
steadily in amount from week to week. A tumor could not be 
demonstrated on physical examination. Soon after the patient died, 
and at the autopsy a carcinoma of the stomach was found upon the 
base of the pyloric ulcer. 

Unfortunately recent investigations have shown that notable 
amounts of lactic acid may also be found in gastric anadeny, and 
in cases of dilatation referable to benign causes. 

Such cases, however, are rare, and it may be safely stated that 
the presence of large amounts of lactic acid will almost invariably 
justify the diagnosis of carcinoma of the stomach, and, according to 
the writer's experience, Boas' test is at least as important asWidal's 



156 CLINICAL DIAGNOSIS. 

seram-test for typhoid fever. Negative results, however, do not 
exclude the existence of the disease. 

Chemically the formation of lactic acid from starch may be repre- 
sented by the following equations: 

I. 2C 6 H 10 O 5 + H 2 = C 12 H 22 O u (milk sugar). 
II. C 12 H 22 O u + H 2 = 2C.5 H 12 6 (glucose). 
III. 2C 6 H 12 6 =r4C 3 H 6 03 (lactic acid). 

It should, finally, be mentioued that only that form of lactic acid 
which results from fermentative processes is of interest in this con- 
nection, and not the sarcolactic acid contained in meat — a point 
which interferes with the general usefulness of BiegePs test-meal. 

Tests for Lactic Acid. For the reasons indicated Boas' test- 
meal (see p. 114) should be employed whenever it is desired to test 
for lactic acid in the gastric contents. If the case under examina- 
tion shows well-marked symptoms of stagnation of the gastric con- 
tents, the stomach should be washed out completely in the evening, 
the soup given then, and the gastric contents procured the next 
morning, before any food or liquid is taken. Otherwise the test- 
meal may be given in the morning on an empty stomach, without 
previous lavage, and the contents examined one hour later. 

Uffelm Ann's Test. Heretofore Uffelmann's reagent was quite 
constantly employed in testing for lactic acid, but everyone who has 
had occasion to make frequent use of this reagent in clinical work 
must have been struck with the unreliability of the results so often 
obtained. In a large majority of the cases thus examined, particu- 
larly if Ewald's test-breakfast is employed, a characteristic reaction 
— i. <?., the occurrence of a lemon or canary-yellow color — is not 
seen, notwithstanding the presence of lactic acid, but a pale-yellow, 
brownish, grayish- white, or even gray color obtained instead, often 
leaving it doubtful whether lactic acid be present or not. Aside 
from doubtful results, the value of the test is greatly diminished by 
the facts that glucose, acid phosphates, butyric acid, and alcohol 
give the same reaction, and that in the presence of such amounts 
of HC1 as are found at the height of normal digestion lactic acid is 
not indicated by the reagent. All these difficulties have long been 
appreciated, and in order to obviate at least some of them it was 
proposed to apply the test to an aqueous solution of the ethereal 
extract of the gastric contents: 

To this end 5 to 10 c.c. of the filtered gastric juice are extracted 
by shaking with from 50 to 100 c.c. of neutral sulphuric ether in 



THE GASTRIC JUICE AND GASTRIC QONTEJs VS. 157 

a stoppered separating funnel for about twenty to thirty minutes, 

and the ethereal extract evaporated over a water-bath, or the ether 
distilled off (no flame). The residue is then taken up with from 5 
to 10 c.e. of distilled water, and tested as follows: Three drops of a 
saturated aqueous solution of the sesquichloride of iron are mixed 
with three drops of a concentrated solution of pure carbolic acid 
and diluted with water until an amethyst-blue color is obtained. 
To this solution a portion of the ethereal extract is added, when in 
the presence of only 0.1 per cent, of lactic acid a lemon or canary- 
yellow color is obtained. 

Selling's Method. Five to ten c.c. of gastric juice are diluted 
from ten to twenty times with water and treated with one or two 
drops of a 5 per cent, aqueous solution of the sesquichloride of iron. 
In the presence of lactic acid a distinct green color is obtained if 
the tube be held to the light. This test is more reliable thau that 
of Uffelmann, as a positive reaction is only obtained in the presence 
of lactic acid. 

Strauss' Method. Instead of evaporating the ether as in the 
above method, the ethereal extract may be directly examined by 

Fig. 33. 




Strauss' apparatus for the approximative estimation of lactic acid. 

shaking with a freshly prepared solution of the sesquichloride of 
iron, as suggested by Fleischer. Making use of this principle 
Strauss has recently constructed an apparatus (Fig. 33) which may 
be found very convenient and which permits of roughly determining 
the amount of lactic acid present. The instrument is essentially a 
separating-funnel of 30 c.c. capacity, bearing two marks, of which 
the one corresponds to 5 c.c, the other to 25 c.c. The apparatus 
is filled with gastric juice to the mark 5, when ether is added to the 
25 c.c. line. After shaking thoroughly the separated liquids are 
allowed to escape by opening the stopcock until the 5 c.c. mark is 
reached. Distilled water is then added to the 25 mark, and the 
mixture treated with two drops of the officinal tincture of the 
sesquichloride of iron, diluted in the proportion of 1 : 10. Upon 



158 CLINICAL DIAGNOSIS. 

shaking the water will assume an intensely green color if more than 
1 p. m. of lactic acid be present, while a pale green is obtained in 
the presence of from 0.5 to 1 p. m. The tincture of iron should be 
kept in a dark-colored dropping-bottle of about 50 c.c. capacity. 

It will be observed that only large amounts of lactic acid, which 
are alone of importance from a diagnostic point of view, are indi- 
cated by the apparatus. Small amounts, as those introduced with 
Ewald's test-breakfast, or referable to lactic-acid fermentation in 
the mouth, are not indicated, so that confusion as to the presence 
or absence of the acid can never arise. 

Boas' Method. In doubtful cases the following method should 
be employed, as with it, following the exhibition of Boas 7 test-meal, 
all possible errors already referred to can be avoided. 

Principle of the method : When a solution of lactic acid is treated 
with a strong oxidizing agent and heated the lactic acid is decom- 
posed into acetic aldehyde and formic acid, according to the equa- 
tion : 

CH 3 — CH(OH) — CO. OH == CH 3 .CHO + H.CO.OH. 
Lactic acid. Acetic aldehyde. Formic acid. 

Practically, then, the test for lactic acid resolves itself into a test 
for acetic aldehyde, which can be readily recognized by testing with 
various reagents, and notably so with Messier' s reagent. This is 
prepared as follows: Two grammes of potassium iodide are dissolved 
in 50 c.c. of water and treated with iodide of mercury, while heat- 
ing, until some of the latter remains undissolved. Upon cooling 
the solution is diluted with 20 c.c. of water. Two parts of this 
solution are then treated with 3 parts of a concentrated solution of 
potassium hydrate; any precipitate that may have formed is filtered 
off and the reagent kept in a well-stoppered bottle. When aldehyde 
is added to such a solution a yellowish-reel or red precipitate results, 
the exact color depending upon the amount of aldehyde present. 
One part of the aldehyde may still be recognized when diluted with 
40,000 parts of water. 

An alkaline solution of iodo-potassic iodide may also be advan- 
tageously used. With this solution aldehyde in a dilution of 
1 : 20,000 will still produce a cloudiness, referable to the forma- 
tion of iodoform, which is readily recognized by its characteristic 
odor (Lieben's test for acetone). 

Method: The filtered gastric juice is tested for the presence of 
free acids with Congo-red (see p. 129). If present, from 10 to 20 



THE UASTBIC JUICE AM) GASTRIC CONTENTS. 159 

c.c. are evaporated to a syrup on a water-bath, after the addition of 

an excess of barium carbonate, while the latter is unnecessary in 
the absence of free acids. The syrup is treated with a few drops 
of phosphoric acid, the C0 2 removed by T bringing it to the boiling- 
point once only, when it is allowed to cool and extracted with 100 
v.c. of neutral sulphuric ether (free from alcohol), by shaking for 
half an hour. The layer of ether is poured off after half an hour, 
the ether evaporated (no flame), the residue taken up with 45 c.c. 
of water, shaken and filtered, and finally treated with 5 c.c. of sul- 
phuric acid and a pinch of the dioxide of manganese in an Erlen- 
meyer flask. This is closed with a perforated stopper carrying 
a glass tube bent to an obtuse angle, the longer limb of which passes 
into a narrow glass cylinder containing from 5 to 10 c.c. of ISTessler's 
reagent or a like quantity of an alkaline solution of iodo-potassic 
iodide. If heat be now carefully applied, the aldehyde, formed by 
the oxidation of the lactic acid with Mn0 2 and H 2 S0 4 , passes over 
when the boiling-point is reached, causing the precipitation of yel- 
lowish-red aldehyde of mercury in the tube containing theNessler's 
reagent, or of iodoform if the alkaline solution of iodine be employed. 
The test is an accurate one. 

Quantitative Estimation of Lactic Acid According- to Boas' 
Method. The principle already set forth also applies to the quan- 
titative estimation of lactic acid. 

Solutions required : 

1. A one-tenth normal solution of iodine. 

2. A one-tenth normal solution of sodium arsenite. 

3. Hydrochloric acid (sp. gr. 1.018). 

4. A potassium hydrate solution (56 : 1 000). 
Preparation of these solutions : 

1. A normal solution of iodine should contain 126.53 (mol. weight 
of iodine) grammes of iodine in the litre, and a one-tenth normal 
solution, hence, 12.6 grammes. In order to dissolve the iodine 
25 grammes of potassium iodide are dissolved in about 200 c.c. of 
distilled water and the 12.6 grammes of resublimed iodine added. 
Distilled water is then added to the 1000 c.c. mark. This solution 
requires no further correction. 

2. The one-tenth normal solution of sodium arsenite is prepared 
by dissolving 19.2 grammes of the salt (mol. weight 191.87) in 
about 900 c.c. of distilled water, when the solution is brought to 
the proper strength by titrating with it a known number of c.c. of 



160 CLINICAL DIAGNOSIS. 

the one-tenth normal solution of iodine, as described below, and 
determining the necessary amount of water to be added. 

Method : 10 to 20 c.c. of the filtered gastric juice are first treated, 
as indicated above, viz., evaporated to a syrup after the previous 
addition of barium carbonate, if free acids be present. A few drops 
of phosphoric acid are added, the C0 2 removed by boiling, and the 
residue extracted on cooling with 100 c.c. of ether free from alcohol; 
the ether is evaporated after separation, the residue taken up with 
45 c.c. of distilled water, and treated with H 2 S0 4 and Mn0 2 . The 
flask is closed by a doubly perforated stopper; through one aperture 
a bent tube passes to the distilling- apparatus, and a straight tube 
provided with a piece of rubber tubing, clamped off, through the 
other. The mixture is then distilled until about four-fifths of the 
contents have passed over, excessive heat being carefully avoided, 
as otherwise the aldehyde will be decomposed, according to the 
equations : 

I. CH 3 — CH(OH) — CO. OH = CH,.CHO + HCOOH. 

Lactic acid. Aldehyde. Formic acid. 

II. CH 3 .CHO + HCOOH + 20 = CH 3 .COOH + C0 2 + H 2 0. 
Aldehyde. Formic acid. Acetic acid. 

To the distillate, which is best received in a high Erlenmeyer 
flask, well stoppered, 20 c.c. of the one- tenth normal solution of 
iodine are added, mixed with 20 c.c. of the 5.6 per cent, solution 
of potassium hydrate. The mixture is shaken thoroughly and 
allowed to stand for a few minutes. In order to liberate the 
hypiodite and the iodine in combination with potassium, not used 
in the reaction, 20 c.c. of HC1 and an excess of sodium bicarbonate 
in substance — some of the latter should remain undissolved at the 
bottom — are added, and the excess of iodine determined by titra- 
tion with the one-tenth normal solution of sodium arsenite. The 
titration is carried to the point of decolorization, when freshly pre- 
pared starch solution is added, and the mixture again titrated with 
the one-tenth normal solution of iodine until the blue color is per- 
manent. The number of c.c. of the one-tenth normal solution 
employed, viz., 20, minus the number of c.c. of the one-tenth 
normal solution of Na 3 As0 3 , will then indicate the number of c.c. 
of the former required in the formation of iodoform, viz., the 
amount of lactic acid present in 10 or 20 c.c. of gastric juice, as 
the case may be. As 1 c.c. of the one-tenth normal solution of 
iodine has been found to indicate the presence of 0.003388 gramme 



Till: GASTRIC JUICE AND GASTRIC CONTENTS. 161 

of lactic arid, it is only necessary to multiply the number of c.c. 
used bv this figure, and the result by 10, in order to obtain the 
percentage. 

The method described is reliable and sufficiently accurate for 
clinical purposes. At the same time it may be said that no more 
time is required than in an ordinary quantitative estimation of 
sugar by means of Fehling's method, or of HC1 according to the 
method of Martins and Liittke. 

Boas' rapid method : This method is less accurate than the pre- 
ceding, but may be advantageously employed in the absence of the 
various reagents necessary with the former. Ten c.c. of filtered 
gastric juice are treated with a few drops of dilute H 2 S0 4 and the 
albumin present removed by heat. The filtrate is evaporated to 
a syrup on a water-bath, water added to the original amount, and 
this again evaporated to a small volume, fatty acids being thereby 
removed. The lactic acid remaining is now extracted with ether 
(200 c.c. for every 10 c.c. of the gastric juice), the ether evapor- 
ated, the residue taken up with water, and titrated with a one-tenth 
normal solution of XaOH, using phenolphthalein as an indicator. 
As 40 parts by weight of NaOH (mol. weight) combine with 90 
parts by weight of lactic acid (mol. weight), and as 1 c.c. of the 
one tenth normal solution of JNTaOH contains 0.004 gramme of 
NaOH, the amount of lactic acid corresponding to the latter is 
found from the equation: 40 : 90 : : 0.004 : x; 40 x = 0.360 ; x = 
0.009. The value of 1 c.c. of the one-tenth normal solution in 
terms of C 3 H 6 3 is thus 0.009. By multiplying the number of c.c. 
used by this figure the amount of lactic acid present in 10 c.c. of 
gastric juice is readily determined. The result multiplied by 10 
will indicate the percentage. 

The Fatty Acids. 

Mode of Formation and Clinical Significance. Unless much 
milk or carbohydrates have been ingested, fatty acids do not occur 
in the gastric contents under physiologic conditions, and it would 
appear from the researches of Boas that their formation is intimately 
associated with that of lactic acid. After the exhibition of his test- 
meal (see p. 154) he was unable to demonstrate their presence either 
in normal conditions or in various diseases of the stomach, such as 
chronic gastritis, atony, or dilatation referable to benign causes, etc. 

11 



162 CLISICAL BIAGNC SIS 

In carcinoma fatty acids, just as lactic acid, were quite constantly 
found. 

That butyric acid can be derived from lactic acid has been demon- 
strated for milk by Fliigge, the reaction taking place according to 
the equation : 

This observation is probably explained by the fact that most of the 
organisms causing butyric-acid fermentation are anaerobic, while 
the bacillus acidi lactici and the oidium lactis at the same time 
eagerly absorb oxygen. 

Acetic-acid fermentation, on the other hand, presupposes the pres- 
ence of alcohol, whether this be introduced into the stomach as such 
or the result of the action of yeast ^saecharomyces eerevisise) upon 
sugar, the transformation of alcohol into acetic acid being repre- 
sented by the equation : 

C 2 H 5 OH — 20 = CH 4 (X — HA 

while the formation of alcohol during the process of fermentation 
from glucose is shown below : 

L CgH^Og -f 2H,0 = 2C 2 H 6 - 2HX0 3 . 
H. 2HX0 3 = 2H,0 — 2C0 2 . 

It is, hence, necessary, whenever acetic acid is met with in the 
gastric contents, to exclude the existence of alcoholism, as it is only 
then permissible to refer its presence to stagnation and advanced 
decomposition of carbohydrates. 

If the examination be confined to an analysis of the gastric con- 
tents, obtained otherwise than after the exhibition of Boas' or even 
Ewald's test-meal, the diagnosis of pyloric stenosis with dilatation 
is probably always justifiable in the presence of notable quantities 
of butyric acid and acetic acid, while the same observations after a 
previous washing out of the stomach and the exhibition of Boas 
test-meal would more strongly suggest carcinoma as the cause of 
the stent - - 

That butyric acicl may occur in the gastric contents when butter 
or fats in general have been ingested is, of course, not surprising. 
and its presence then should be looked upon as a physiologic occur- 
rence. At the same time it should not be forgotten that butyric 
acid, just as lactic acid, may possibly have been formed in the 
mouth, and conclusions should, hence, only be drawn when such 



THE GASTRIC JUICE AND aASTRIC CONTENTS. 163 

sources of error can be definitely excluded and the amount found 
exceed- mere traces. 

In conclusion, it may be said that in pathologic conditions butyric 
acid is far more frequently encountered in the gastric contents than 
acetic acid, while the significance of the two in the absence of alco- 
holism is the same. 

Tests for Butyric Acid. 1. Butyric acid can usually be recog- 
nized by its odor alone, which is that of rancid butter. Often, 
however, it will be necessary to resort to more definite tests, such 
as the following : 

2. Ten c.c. of filtered gastric juice are extracted with 50 c.c. of 
ether. The ether is evaporated and the residue taken up with a 
few c.c. of water. If a trace of calcium chloride in substance be 
now added, the butyric acid will separate out in the form of small 
oil-droplets, the nature of which is readily recognized by their 
pungent odor. If, instead of adding calcium chloride, a slight 
excess of baryta-w r ater is used, strongly refractive rhombic plates 
or granular, wart-like masses of barium butyrate are obtained upon 
evaporation. 

Tests for Acetic Acid. 1. Like butyric acid, acetic acid can 
usually be recognized by its odor. 

2. Ten c.c. of filtered gastric juice are extracted with ether. The 
ether is evaporated, the residue dissolved in a few drops of water, 
and accurately neutralized with a dilute solution of NaOH, sodium 
acetate being formed. If to this a drop or two of a very dilute 
solution of the perchloride of iron be added, a dark-red color results 
in the presence of acetic acid. With nitrate of silver a precipitate 
is obtained which is soluble in hot water. 

Quantitative Estimation of the Patty Acids. Method of 
Cab n-Meh ring, modified by McNaught : The total acidity is deter- 
mined in 10 c.c. of filtered gastric juice, and the acidity obtained, 
upon titration of another 10 c.c, after evaporation to a syrup, sub- 
tracted from the former, the difference giving the acidity referable 
to fatty acids. 

Quantitative Estimation of the Organic Acids. Method of 
Hehner-Seemann : This method is based upon the observation that 
if a certain amount of a one-tenth normal solution of NaOH 
be added to organic acids and the mixture be evaporated and in- 
cinerated, the organic acids escape as C0 2 , leaving their alkali 
behind in the form of a carbonate, the amount of which can be 



164 CLINICAL DIAGNOSIS. 

determined by titrating with a one tenth normal solution of HC1. 
The amount of physiologically active HC1 can be determined at the 
same time by deducting from the total acidity the acidity referable 
to organic acids. 

Method: 10 or 20 c.c. of filtered gastric juice are neutralized 
with a one-tenth normal solution of XaOH, evaporated to dryness, 
and incinerated, the application of heat being discontinued as soon 
as the ash has ceased to burn with a luminous flame. The residue 
is taken up with water and neutralized with a one-tenth normal 
solution of HO. This is prepared by diluting 146 grammes of 
HO (sp. gr. 1.14) with distilled water to about 900 c.c., when the 
solution is brought to its proper strength by comparing it with a 
one-tenth normal solution of XaOH, according to directions given 
elsewhere. The number of c.c. of the one-tenth normal solution of 
HO employed multiplied by 0.00365 will give the amount of fatty 
acids, in terms of HO, contained in the 10 c.c. of gastric juice, from 
which the percentage is readily calculated by multiplying by 10 or 
5, as the case may be. By deducting the number of c. c. employed 
from that of the one-tenth normal solution of XaOH first used the 
number of c.c. of the latter required for the neutralization of the 
physiologically active HO is ascertained, and the amount of the 
HO determined by multiplying by 0.00365. 

Gases. 

The stomach always contains a certain quantity of gases which 
have partly been swallowed and partly passed into the stomach 
from the duodenum. As fermentative processes in physiologic 
conditions occur only when carbohydrates or fats have been in- 
gested, and then only to a slight degree, nitrogen, oxvgen, and 
carbon dioxide are the only gases found during the process of albu- 
minous digestion. As the oxygen swallowed is, moreover, largelv 
absorbed by the blood, and two volumes of carbon dioxide are re- 
turned for one volume of oxygen, the presence of large amounts of 
the former and small amounts of the latter is readily explained. 
In an analysis of the gases contained in the stomach of a dog which 
had been fed on meat Planer found the following proportions : 

CO., "25.2 vol. per cent. 

O 6.1 - " 

X 68.7 • 



THE aASTRIC JUKI- AND CASTRIC CONTENTS. 165 

With a strictly vegetable diet, on the other hand, hydrogen may 

also be found (Planer): 





.Mill 


i. 


Dog. 


CO 


. 20.79 


33.83 


32.9 vol. per cent. 







0.37 


0.8 " " 


N 


. 72.50 


;5S.22 


66.3 " 


II 


. 6.71 


27.58 





The presence of H is readily understood if it be remembered that 
during the process of butyric-acid fermentation H and C0 2 are 
formed. Lactic-acid or acetic-acid fermentation does not give rise 
to the formation of gases. 

Marsh gas, CH 4 , a product of the fermentation of cellulose, may 
also be found in pathologic conditions, formed according to the 
equation : 

(C 6 H 10 O 5 )n + (H 2 0)n = 3(C0 2 )n + 3(CH>. 

It is yet an open question whether CH 4 is formed in the stomach or 
passes into the stomach from the small intestine. 

Such observations must, however, be regarded as rarities. In 
one case of this kind, examined by Ewald and Ruppstein, in which 
alcohol, acetic acid, lactic acid, and butyric acid were found in the 
vomited material, an analysis of the gases gave the following result : 

CO, 20.6 vol. per cent. 

O 6.5 " 

N 41.4 " 

H 20.6 " 

CH, 10.8 •' 

Traces of olefiant gas and of sulphuretted hydrogen were also 
found. It is curious to note that in this case the patient, who, 
according to his own statement, had " acetic acid works in his 
stomach on one day and gas works on another day/' was occasion- 
ally able to light the eructated gas at the end of a cigar-holder, 
where it burnt with a faintly luminous flame. McNaught has 
reported a similar case, in which the analysis furnished the follow- 
ing results: C0 2 = 56 per cent.; H = 28 per cent.; CH, = 6.8 
per cent.; atmospheric air =9.2 per cent. 

Ammonia and sulphuretted hydrogen are also at times met with, 
and are always due to albuminous putrefaction. 

Boas found that sulphuretted hydrogen is quite commonly present 
in cases of dilatation referable to benign causes, while it is almost 
always absent in carcinoma. He adds that it is never found when 



166 CLIXICAL DIAGXOSIS. 

tic acid is present. In acute gastritis it may be temporarily 
served. In a number : ises of carcinoma the writer never 

found sulphuretted hydrogen. In one case reported by Strauss the 
bacillus coli communis was apparently concerned in its production. 

To obtain a knowledge of the gases formed in the stomach during 
the process of digestion it is only necessary to rill an ordinary 
Doremus ? ureometer, or an Einhorn's saeeharirneter. with the 
unfiltered gastric contents, and to keep it at a temperature of from 
37 : to 47 : C.j when the evolution of gas san be closely followed 
and the necessary tests made. The presence of CO ; is readily 
recognized by passing a small amount of XaOH. in concentrated 
solution or in substance, into the tube, after the evolution has 
entirely ceased, when the fluid will rise. If other gases be present 
at the same time, they will remain after the CO : has been absorbed. 
ELjS is readily recognized by its odor and by the fact that it will 
color a piece of filter-paper moistened with a few drops of NaOH 
and acetate of lead a more or less prone meed brown. The test is 
conveniently made by filling a test-tube about half-full with the 
gastric contents and closing it with a eork-stopper to which a strip 
o: leal-paper, prepared as ::: ..:.■;.:-.- ... > fastened. 

The eructation of gas formed in the stomach should not be con- 
founded with the so-called eructa ..v. in which either no gas 
is eructated, or air simply enters the oesophagus and is expelled 
again with a loud, explosive n nse. This may be frequently observed 
in neurasthenic and hysterical individuals, and is to a greater or 
less degree under the control of the will. It is hardly likely, how- 
ever, that the physician will be called upon in the laboratory to 
differentiate between this form and that of true ructus caused by 
fermentative processes taking place in the stomach. The gases 
brought up in the former conditions are without odor or taste, and 
thus differ from those found in true dyspepsia 

Acetone. 

The : ne in the gastric contents in pathologic con- 

ditions has been repeatedly observed, especially by v. Jaksch and 
Lorenz, and it is curious to note that the latter was at times able to 
demonstrate larger quantities of the substance in the gastric contents 
than in the urine. 

In the chapter on Acetonuria the relation exi-rhu between climes- 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 167 

tive diseases and the elimination of acetone will be dealt with more 
fully, but it may here be mentioned that in the "primary" dis- 
eases of the gastro-intestirial tract acetone is quite constantly met 
Avitli in the gastric contents, while it is but rarely observed in the 
secondary forms, and never seen in the gastric neuroses. 

This statement, however, is denied by Sovelieff, who claims to 
have found traces of acetone only in one case of nervous dyspepsia, 
while negative results were obtained in all other diseases of the 
stomach. The writer has repeatedly been able to demonstrate the 
presence of acetone in cases of carcinoma of the stomach, and has 
never found it in neurotic conditions. 

In order to test for acetone the gastric contents are distilled after 
the previous addition of a small amount of phosphoric acid (1 : 1000), 
so as to prevent an excessive evolution of gases, and the tests of 
Reynolds and Gunning (see Urine) applied to the distillate. If 
both reactions furnish a positive result, the presence of acetone may 
be regarded as demonstrated. 

Ptomaines and Toxalbumins. 

Remembering that ptomaines and toxalbumins have been directly 
obtained from tainted meat, sausage, fish, clams, crabs, cheese, etc., 
it is probable and, indeed, to be expected that these bodies should 
be present in the gastric contents also. At the same time it may 
be mentioned that the stomach appears to possess the power of 
eliminating from the system poisons of this nature which are circu- 
lating in the blood. This is shown by the observations of Alt, who 
found that the water with which the stomach of an animal had been 
irrigated after the subcutaneous injection of the poison of Pelias 
berus and Echidna arictans, or the direct bite of the snake, pro- 
duced the same symptoms of poisoning when injected into another 
animal. It is interesting to note that with lavage of the stomach 
the poisoned animal recovered. Similar observations have been 
made in cholera Asiatica. Certain vegetable alkaloids, such as mor- 
phine, are also known to be eliminated to a large extent by the 
stomach. 

Vomited Material. 

Food-material. The vomiting of large amounts of totally undi- 
gested meat two to three hours after its ingestion is a rare occur- 
rence, and is onlv met with in conditions associated with an entire 



168 



CLINICAL DIAGNOSIS. 



absence of digestive power in the stomach — i. e., in cases of atrophic 
cirrhosis of the stomach (anadenyof Ewald). This condition is not 
to be confounded with the regurgitation of undigested food, mixed 
with mucus and saliva, seen in cases of stricture of the oesophagus 
or of the cardiac orifice of the stomach. While at the outset of the 
latter disease the regurgitation of food occurs immediately or at 
least very soon after a meal, it may take place between meals in 
the later stages of the disease. The recognition of the origin of the 
material brought up may then be exceedingly difficult. In such 
cases an examination should be made for biliary coloring-matter, 
which, if present, will, of course, immediately exclude the oesoph- 
agus as the source of the material ejected. Unfortunately, how- 
ever, the reverse does not hold good. Small amounts of undigested 
meat are of no significance. 



Fig. 34. 







Collective view of vomited matter. (Eyepiece III., objective 8 A., Reichert ) a, muscle-fibres ; 
b, white blood-corpuscles ; c, c', squamous epithelium ; c", columnar epithelium ; d, starch- 
grains, mostly changed by the action of the digestive juices ; e, fat-globules ; /, sarcinae ven- 
triculi ; g, yeast-fungi ; h. forms resembling the comma-bacillus found by the author once in the 
vomit of intestinal obstruction ; i, various micro-organisms, such as bacilli and micrococci ; 
k, fat-needles, between them connective-tissue derived from the food ; I, vegetable cells. 

(V. JAKSCH.) 



The vomiting of well-digested food is observed in some of the 
neuroses of the stomach, and also in certain cases of acute and 
subacute gastritis, ulcer of the stomach, and chronic gastritis in its 
early stages. The vomiting referable to cerebral and spinal dis- 
eases also belongs to this category. 



THE GASTRIC JUICE AM) GASTRIC CONTENTS. [69 

In this connection it is very important to inquire into bhe exist- 
ence of nausea previous to the vomiting, for, as is well known, 
considerable amounts of saliva and mucus may be swallowed if 

much nausea has existed, the result being that the process of diges- 
tion is arrested before the occurrence of vomiting, when it would be 
entirely erroneous to conclude that, because the material ejected 
has not reached that stage of digestion which should be expected 
at the time of the vomiting, the stomach is incapable of properly 
performing its functions. 

Mucus. The constant presence of large amounts of mnens in 
the gastric contents, obtained with the stomach-tube, is almost path- 
ognomonic of the mncons form of gastritis, while its presence in 
vomited matter may be referable to its having been swallowed, 
owing to pre-existent nausea. In cases of pharyngitis moderate 
amounts of mncus are frequently found. The vomiting of pure 
mucus, according to Boas, is always pathognomonic of the absence 
of dilatation of the stomach, a statement founded on reason, as it is 
altogether unlikely that no particles of food should be brought up 
at the same time. 

Under the term gastrosuccorrhoea mucosa Dauber has recently 
described a condition in which large amounts of mucus are secreted 
by the non-digesting organ in the absence of any symptoms pointing 
to a gastritis. The writer has observed a similar case occurring in 
a neurasthenic patient, in which enormous quantities of mucus could 
at times be obtained from the fasting organ, but never during the 
process of digestion. A mild degree of hyperchlorhydria existed 
at the same time, as well as enteritis mucosa and rhinitis mucosa. 
The motor power was practically normal. 

Mucus is readily recognized on simple inspection by its glossy 
appearance. Chemically it is distinguished by its behavior toward 
acetic acid. (See Urine.) 

Saliva. The vomiting of pure saliva in the morning upon rising 
is a fairly common symptom of chronic pharyngitis, which in turn 
frequently carries in its trail a chronic gastritis, constituting the 
so-called vomitus matutinus. Saliva, like mucus, is, of course, 
always present in the gastric contents in small amounts. Larger 
amounts are usually referable to an increased secretion and a swal- 
lowing of the same, owing to the existence of nausea. Chemically, 
saliva is best recognized by testing for the presence of the sulpho- 
cyanides (see Saliva, p. 102). 



170 CLINICAL DIAGNOSIS. 

Bile. Bile is rarely observed in the gastric contents brought up by 
the stomach-tube, but is frequently seen in vomited matter, of which 
it may be said to be a constant constituent whenever the vomiting 
has been very intense or frequently repeated. Its presence in the 
former case should always excite suspicion of the existence of a 
stenosis of the descending or horizontal portion of the duodenum, 
or the beginning of the jejunum. This diagnosis becomes the more 
probable the more constant its presence. 

Pancreatic Juice. Mixed with bile, there is probably always 
present some pancreatic juice, and it has even been suggested that 
the constant absence of the constituents of this, associated with the 
presence of bile, is strongly suggestive of pancreatic disease or of 
obstruction of the pancreatic duct (the ductus Wirsungianus). 

Blood. The presence of unaltered blood in the gastric contents 
is usually recognized without difficulty. As marked alterations in 
color, varying from a deep red to a coffee or chocolate brown may 
occur, however, when free acids are present, it is at times neces- 
sary to resort to a more detailed examination. In order to recog- 
nize mere traces, when the macroscopic and even the microscopic 
examination do not point to the presence of blood, the method of 
Miiller and Weber should be employed. Kuttner claims that he 
was thus able to demonstrate the presence of blood in numerous 
cases of chlorosis, in which other tests only furnished negative re- 
sults. The writer has been less successful in the disease in question, 
but admits that in cases of carcinoma and ulcer of the stomach it is 
with this method often possible to find traces of blood which would 
otherwise have remained unnoticed. 

Method of Miiller and Weber : The gastric contents are treated 
with a few c.c. of concentrated acetic acid and extracted with ether. 
Should the ether not separate out in a clear layer after a few min- 
utes, a few drops of alcohol are added. If the ether then remains 
colorless, no blood-pigment is present, while a brownish-red color 
indicates the presence of acetate of hrematin. As a similar but 
yellowish-brown and much less intense discoloration of the ether 
may be produced by other pigments, such as biliary coloring-matter, 
it is well in doubtful cases to test the ethereal extract with tincture 
of guaiacum. A positive result indicates the presence of blood 
coloring-matter. The same may be said if, upon spectroscopic ex- 
amination of the ethereal extract, an absorption-band is discovered 
at the junction of the red and yellow. 



THE GASTRIC JUICE AM) (,'ASTRIC CONTENTS. 171 

Hemorrhage from the stomach, hcematemesis, may be observed in 
the most diverse conditions, being either dependent upon a primary 
disease of the organ, such as ulcer and carcinoma, or occurring 
secondarily to diseases of other organs, leading to a hypersemic con- 
dition of the gastric mucosa, such as the various forms of cardiac, 
renal, and hepatic disease, in connection with menstrual abnormali- 
ties, etc In melaena, purpura hemorrhagica, pernicious anaemia, 
etc., the cause of the hemorrhage cannot always be determined. It 
appears to be certain, however, that nervous influences may also 
take part in the causation of gastric hemorrhage. 

Pus. The occurrence of pus in the vomited matter, referable to 
disease of the stomach itself, is quite rare, and practically only seen 
in cases of phlegmonous and diphtheritic gastritis. More frequently 
it indicates the perforation into the stomach of an accumulation of 
pus from a neighboring organ. An abscess of the liver, a suppura- 
tive pancreatitis, an abscess of the colon, may thus prove to be the 
primary source of the pus. When present in considerable amount 
pus is, of course, readily detected by the naked eye; if any doubt 
should arise, a microscopic examination will determine the ques- 
tion. 

Stercoraceous Material. Very important from a clinical stand- 
point is the vomiting of stercoraceous matter, which is notably ob- 
served in cases of ileus. This is usually recognized without diffi- 
culty by its odor, which is referable to the presence of skatol. If, 
however, any doubt should arise, it is only necessary to distil the 
vomited matter after the addition of a little phosphoric acid, and to 
test for the presence of phenol, indol, and skatol in the distillate, as 
described in the'ehapter on Feces (see p. 192). When chiefly derived 
from the small intestine the vomited matter, according to v. Jaksch, 
will contain bile-acids and bile-pigment together with an abundance 
of fat, which may be detected by chemical or microscopic examina- 
tion. The reaction is usually alkaline or feebly acid. 

Recently the author had occasion to examine the vomited matter 
of a patient in whom an almost complete obstruction existed imme- 
diately above the ileo-caecal valve; the color of the material was 
a golden-yellow, the reaction neutral; no bile-pigments or biliary 
acids were found, while hydrobilirubin was demonstrated. Formed 
masses of feces, if found at all in the vomited matter under such 
conditions, are certainly of extreme rarity. 

Parasites. Of parasites, ascarides, segments of taenia?, trichinae, 



172 CLISICAL DlAGyOSLS. 

anchylostonia duodenale, and oxyuris vermicularis are, at times, 
enr-'iuntere':]. ::: ■;. :ies:-rip:::-n :: ^i:::-h s~r :::e i-L^pier :-n Feces, 

The Odor. But little information, as a rule, is derived from the 
odor of the gastric contents. The odor of normal gastric juice is 
quite characteristic, suggesting the presence of some acid, which can 
be sharply distinguished, however, from the well-known odor refer- 
able to acetic acid or butyric acid. If blood be present in large 
amounts, the vomited matter emits an odor which is so character- 
istic as never to be mistaken. A feculent odor is met with in cases 
of enterostenosis, or in the presence of an abnormal communication 
between the stomach and the small or large intestine. A putrid 
odor may be observed in cases of ulcerative carcinoma, pyloric 
stenosis referable to ulcer, simple carcinoma of the stomach, mus- 
cular hypertrophy of the pylorus, stenosis due to inflammatory 
inhesions. e:c. 

It may finally be mentioned that in cases of phosphorus-poisoning 
the vomited matter emits an odor of garlic; the odor observed in 
tmemic conditions is referable to ammonia; a carbolic-acid odor is 
met with in cases of poisoning with this substance. 

MICROSCOPIC EXAMINATION OF THE GASTRIC 
CONTENTS. 

In the gastric juice obtained from the non-digesting stomach the 

rions morphologic constituents of mucus an saliva, which have 
been des:-r:be:l ~~.~r~^--r. -ir ::'.;i::, M::ros:-:-p::- per:::~r- e: foofi. 
such as elastic tissue-fibres, starch-granules, fat-droplets, ratty acid 
rystals, vegetable and muscle fibres, are, furthermore, quite con- 
stantly seen. Leucocytes and isolated nuclei are also observed; 
the latter are set free by the action of the gastric juice upon niue : - 
corpuscles and epithelial cells. 

If gastric juice be allowed to stand, small tapioca-like bodies will 
collect at the bottom of the vessel, which upon microscopic exami- 
nation will be seen to contain numerous snail-shell-like formations, 
occurring either singly or collected in groups. These probably con- 
sist of altered mucin, as they can be artificially produced by adding 

sum -mount of dilute HC1 to saliva. According to Boas, 

are of no diagnostic significance. 

Epithelial cells, fragments of the epithelial lining of the du sts : 
glands, as well as goblet-cells, are not infrequently met with in the 



PLATE 




\\' s ' ; 



3* 







The Boas-Oppler B? ene Blue. From a Case 

. arcinoma of the Large Curvature of the Stomach. 
Personal Obser 



THE GASTRIC JUICE AND GASTRIC CONTENTS, 173 

juice obtained from the non-digesting organ. In addition to these 
constituents various micro-organisms, such as the Leptothris buo- 

oalis, bacillus subtilis, saecharomyces, micrococci, often arranged in 
the form of tetrahedra, Clostridium butyrieum, etc., may be encoun- 
tered. 

Among the bacteria which may be found in the gastric contents 
under pathologic conditions the bacillus, described by Boas and 
Oppler, is undoubtedly the most interesting and has of late attracted 
much attention. It appears to be present quite constantly in car- 
cinoma and is almost always absent in other diseases of the stomach. 
It is thought that the formation of lactic acid, which is likewise so 
constantly observed in carcinoma, is largely and perhaps solely 
referable to its presence. The organism in question (Plate VII.) 
is non-motile, and essentially characterized by its great length and 
by the fact that the individual bacilli are frequently seen joined to- 
gether end to end, forming long threads and zig-zag lines, which 
are quite characteristic. Often the entire field of vision is filled 
with dense conglomerations. Cultivation -experiments have thus 
far not been successful. The organism is readily stained with the 
usual aniline-dyes. 

In vomited material containing biliary coloring-matter, leucin, 
tyrosiu, and cholesteriu are also quite commonly observed, and may 
be recognized by the form of their crystals, as well as their chemical 
reactions, described elsewhere. 

In pathologic conditions sarcinse, blood, pus, shreds of the mucous 
membrane of the stomach, carcinomatous material, etc., may also be 
present. 

Sarcince (Fig. 34) occur in the form of peculiar colonies of cocci, 
arranged in squares or tetrahedra, strongly resembling cotton-bales. 
Not infrequently they are encountered under normal conditions, but 
only in small numbers. In pathologic conditions, on the other 
hand, a drop of the gastric contents may constitute an almost pure 
culture. A case is even on record in which the pylorus had become 
entirely occluded by an inspissated mass of these organisms. When- 
ever present the existence of certain fermentative processes may be 
inferred. 

It is curious to note that in advanced cases of carcinoma of the 
stomach sarcinae are practically never seen, although the conditions 
are certainly most favorable for their development. Oppler was 
unable to find them twenty-four hours after their introduction in 



174 CLINICAL DIAGNOSIS. 

large numbers and in pure culture. In cases of carcinoma of the 
curvatures and the walls, as also in advanced pyloric carcinoma, 
sarcinae were never found, while they may be present in incipient 
cases of pyloric carcinoma as long as hydrochloric acid is still 
secreted. 

The occurrence of blood and pus in the gastric contents has been 
considered (see p. 170). 

It not infrequently happens that small shreds of mucous mem- 
brane are brought away by the stomach-tube, and in cases of 
chronic gastritis, hyperchlorhydria not dependent upon ulcer, and 

Fig. 35. 




Cancer-cells from the gastric contents. (Ewald.) 

in some of the neuroses this is indeed not at all uncommon. Boas 
even suggests that in the latter case, where fragments of mucous 
membrane are so readily detached, this may possibly be etiologi- 
cally connected with the formation of ulcers, and there can be no 
doubt that the mere action of the abdominal muscles exerted during 
the process of defecation may be sufficient to detach such frag- 
ments. From the microscopic appearance of the particles the diag- 
nosis between a gastric neurosis and one of the various forms of 
chronic gastritis may be frequently made, and the same may be 
said to hold good for the differential diagnosis between a true gas- 
tritis and a glandular insufficiency referable to passive congestion 
of the gastric mucosa. 



THE GASTRIC JUICE AND GASTRIC CONTENTS. L75 

Not Infrequently tumor particles are found in the gastric contents. 
In the accompanying illustration (Fig. 35) a specimen obtained from 

Fit;. 36. 




A fragment of mucous membrane derived from the stomach. (Ewald.) 

a carcinomatous patient is represented, which is quite readily dis- 
tinguished from similar fragments of mucous membrane (Fig. 36). 

EXAMINATION OP THE MOTOR POWER OP THE 
STOMACH. 

Under physiologic conditions the stomach should contain but few 
particles of food, or none at all, six hours after the ingestion of 
RiegePs meal, or one and one-half to one and three-quarters hours 
after that of Ewald. A delay in the removal of the gastric con- 
tents may be referable to the existence of a simple atony or to dila- 
tation of the stomach. According to Boas, an atony may usually 
be diagnosed, if, following the exhibition of a supper consisting of 
bread and butter, cold meat, and a large cupful of tea, the stomach 
is found empty in the morning, providing, of course, that symptoms 
exist which point to atony or dilatation. It should be remembered, 
however, that in cases of acute and subacute gastritis, in the ab- 
sence of a more serious lesion, food may be found in the stomach 
twenty-four hours after its ingestion. A dilatation may, on the 
other hand, be diagnosed if the stomach under the same conditions 
contains a considerable amount of food. In such cases it happens 
that not only remnants of the test-supper, but remains of meals 
taken one, two, three, or even more days previously are found. 
The quantities, moreover, which may be obtained at the time of 
the examination are often surprisingly great, and may amount to 
sixteen pounds or more. Portel cites the case of the Due de 



176 CJLIKICAX DIA: .-. 

Chausnes, one of Pa . :_ . : ~ . : . mid 

hold 4.5 liters — i. c E pmts 

The .following method.- mt T be employed:: rtfosjpn 
to motor power miaer. 

IiEEBe's Method. The sroniaei rca flesB ;ur s:r loams 
the ingestion of Riegel & msd\ wi:i aoout 1000 c.c. o: v-.:e: In 
the presence of only __. _ :: > c to nut - - -. Ah 

stomach may be regarded m norma., Tin- hh _ in i tefc% 

the most convene:-: rjpn : :ai imrposes. 

The Saloe Test w Iv___: _.. I : :: Eh - 

upon the observation tod nDd}, a compound etne: flS suic--. 
is only decomposed inti nnenol and salicylic acid in an alkaline 
medium. As the salicylic acid is eliminated in the urn - 

uric acid, it is nossilih i KknrntHtf to finm r. to 
fr.om the stomaex mi; to anuflj intestine. 

A capsule containing one gramme .-:::.' 

immediately after hi it or dinne: wner wytmik j ntfi m 

urine, passed one-ia_:: out n out -vr noriYi anc ~v - 1 — ; m _ 

Adition of a small amnun' l of 

the sesquichloride of iron. In in- ,> : rifcjflimn acid a 

violet color : "Under normal co: _ : : 

obtained after from f orr -•: see • ■- ertig rve minutes & Iirn&a 
delay may usually be regarded as mclicatuij. to :: --.ire o: motor 
insufficiency. If no result h dUiMinei a::e: - : 
pyloric stenosis undoubtedly exists. Untie: norma i ; i 
llteniom: r. will be observed tha: to $bM± dlrmhs : : nj 

^ - ' : ■.-.■■ " _ _ : : : - ._ - : srasi I 

c&vs reaciior mr :_. - tbtainec efffa fiiae 

possible to cL efcwe&i 'i anc :i-- -: :ne stomad. 

The test, whi m^emeiv 

no* i _ ■ - ■. " " . am 

t:ni- he :: .. - ■ no I ¥ w .. totfl - ■ - -■■ : ueran 

b nms k» 3elay©£ n to ht m rang ] :. ■ es begs o: b 
lermenia: i 

EXAMINATION OF THE PoESOPPTTTE PDWJili : 7 THE 

STOMACH. 

:nis end i miainin: .1 grannie E 

. " •: - >efois i nesdl anc to cammed 



THE GASTBIO JUICE AND GASTRIC CONTENTS. 177 

for the presence of potassium iodide at intervals of from two to three 
minutes. (See Saliva, p. 10G.) 

Under normal conditions a violet color is obtained after from sis 
and one-half to eleven minutes, and a bluish tinge after from seven 
and one-half to fifteen minutes. In pathologic conditions a delayed 
reaction is observed in almost all diseases of the stomach, and is 
especially marked in eases of dilatation and carcinoma, less so in 
chronic gastritis, and variable in cases of ulcer. 

Absolute conclusions, however, cannot be drawn from results thus 
obtained, as a normal reaction-time has also been observed in cases 
of dilatation and chronic gastritis. 

INDIRECT EXAMINATION OP THE GASTRIC JUICE. 

Gunzburg's Method. In those cases in which for any reason 
the introduction of the stomach-tube is contraindicated or imprac- 
ticable the following method, suggested by Giinzburg, may be 
employed : 

A tablet of 0.2 to 0.3 gramme of potassium iodide is inserted into 
a piece of the thinnest possible, strongly vulcanized rubber-tubing, 
measuring about 2.5 cm. in length. The ends are folded as shown 
in Fig. 37, and the little package tied with three threads of fibrin 

Fig. 37. 




A fibrin potassium-iodide package of Giinzburg. 

hardened in alcohol. Every package should be examined before 
use, by immersion in warm water for several hours, to determine its 
tightness, testing for the presence of potassium iodide by means of 
starch-paper and fuming nitric acid. One of these packages is 
swallowed by the patient three-quarters to one hour after an 
Ewald's test-breakfast, and the saliva tested for potassium iodide 
at intervals of fifteen minutes, until a positive result is reached, or 
until six hours have elapsed. It is unnecessary to wait longer than 
six hours. In the presence of free HC1 the threads of fibrin are 
dissolved and the potassium iodide absorbed, ruder normal con- 
ditions a positive reaction is obtained after from one to one and 

12 



178 CLINICAL DIAGNOSIS. 

three-quarters hours, while auachlorhydria undoubtedly exists if no 
result is obtained within five to six hours. In eases of hyperchlor- 
hydria and hypochlorhydria the reaction is delayed for more than 
two to three hours. Giinzburg further advises that the resorption- 
test with potassium iodide be also made, and that the reaction-time 
be deducted from that taken up in the elimination of the iodide 
contained in the package. Several tests, moreover, should be made 
in the same case. 

The author has had occasion to experiment with packages obtained 
from Germany and manufactured according to the directions of 
Giinzburg. 1 In most of the packages the threads of fibrin had 
become brittle and were broken in transit. The results obtained 
with about twenty intact specimens, however, were entirely satis- 
factory, and it is to be regretted that the packages cannot as yet 
be obtained in the American market. 

The Author's Test. Recent researches have led the author 
to believe that a close relation exists between the elimination of 
indican in the urine and the amount of free HC1 present in the 
gastric contents. The results reached may be summarized as fol- 
lows : 

1. Euchlorhydria is never associated with an increased elimina- 
tion of indican. 

2. In cases of simple neurotic hyperchlorhydria a subnormal or 
normal amount of indicau is found. 

3. In cases of hyperchlorhydria associated with ulcer an increased 
indicanuria is quite constantly observed. 

4. Auachlorhydria, referable to organic lesions of the stomach, is 
almost invariably associated with a highly increased indicanuria. 

5. Hysterical auachlorhydria may be associated with the elimi- 
nation of a normal or increased amount of indican. 

6. In cases of hypochlorhydria increased indicanuria is the rule. 
Given as premises : 

1. That a resorption of decomposing pus is not taking place any- 
where within the body, as such a process in itself is capable of caus- 
ing an increased elimination of indican. 

2. That a stenosis of the small intestine does not exist. 

3. A normal mixed diet, containing no excessive amounts of red 
meat. 

Gothe, Apotheke, Frankfurt a. M. 






THE GASTRIC JUICE AND GASTRIC CONTENTS, 



179 





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180 CLINICAL DIAGNOSIS. 

Method: The urine of twenty-four hours is carefully collected 
and a specimen taken for examination. A few c.c. of urine are 
mixed with an equal amount of concentrated hydrochloric acid and 
two or three drops of a concentrated solution of sodium hypochlo- 
rite and 1 or 2 c.c. of chloroform added. The mixture is thor- 
oughly agitated and set aside. The indigo which has been liberated 
in this manner is taken up by the chloroform, coloring this blue to 
a greater or less extent, the degree of increase as compared with 
the normal being determined by the intensity of the color obtained. 
For the sake of comparison it is well to employ the same quantities 
of urine and of reagents in every case, marked tubes being very 
convenient for this purpose. 



CHAPTER IV. 

THE FECES. 
DEFINITION. 

The feces may be defined as being a mixture of undigested par- 
ticles of food and unabsorbed secretions of the gastro-intestinal tract, 
together with intestinal mucus, epithelial cells, and bacteria. 

THE EXAMINATION OF NORMAL FECES. 
General Characteristics. 

Number of Stools. The number of stools which may be passed 
in the twenty-four hours is even under physiologic conditions sub- 
ject to wide variations, but usually constant for one and the same 
individual. One or two stools pro die may be regarded as normal. 
Exceptions, however, are frequent. Persons are thus met with who 
have but one stool every two to four days, and cases are on record 
in which one passage only occurred every seven to fourteen days, 
the individuals evidently enjoying perfect health. On the other 
hand, the number of stools may be increased to three and even four 
under strictly normal conditions. Hence the importance of accurately 
ascertaining the habitual number of stools in every individual. It 
would thus be manifestly wrong to regard the passage of three 
stools daily as diarrhoea, or the passage of only one stool in forty- 
eight hours as constipation, if this number has been habitual through- 
out life. 

Whether or not it is permissible to regard as normal those rare 
instances in which one stool only occurs every two to six weeks, 
or even less frequently, appears rather doubtful. 

Amount. Iu those cases in which more than one or two stools 
occur in twenty-four hours it is well to ascertain the amount actu- 
ally passed. The figures given by different observers as expressing 
the total amount vary somewhat, from 100 to 200 grammes being 
about the normal. This quantity is increased by a diet rich in 



182 CLTXICAL DIAGXOSIS. 

vegetable and starchy foods, and diminished by one rich in animal 
proteids, so that 60 and 250 grammes may be regarded as the ex- 
treme limits in health. Such amounts as 500 and 1000 grammes 
are certainly abnormal. 

Consistence and Form. The consistence of a stool depends 
essentially npon the amount of water present, and hence npon the 
character of the food ingested, being softer with a purely vegetable 
diet (80-85 per cent, of water) than with a diet rich in animal pro- 
teids (60-65 per cent."). With a mixed diet the amount of water 
corresponds to about 75 per cent. As a general rule, normal stools 
exhibit the characteristic cylindrical form and are fairly firm. 
Slushy stools, however, are also seen quite frequently, and round, 
scybalous masses, although by far more common in cases of consti- 
pation, may likewise be observed in health. 

Odor. The repugnant odor of the feces is, to a large extent, due 
to the presence of indol and skatol, products of albuminous decom- 
position; sulphuretted hydrogen, methane, and traces of phosphin 
may add still further to their disagreeable odor. 

Color. The color of the feces varies, according to the nature 
of the food ingested, from light to almost a blackish-brown, a firm 
stool being in general darker in color than a thin stool. A stool 
that has remained exposed to the air is also somewhat darker upon 
its outer surface than in its interior, owing to processes of oxidation. 
In nursing-infants, in consequence of the exclusive ingestion of milk, 
the color is light yellow. 

Under normal conditions the color is never due to native biliary 
coloring-matter, the presence of this substance being always indica- 
tive of some pathologic process, but is largely dependent upon the 
presence of hydrobilirubin — L e., reduced bilirubin. It is, further- 
more, influenced by the nature of the food, chlorophyll tending to 
produce a greenish color, starches a yellowish tinge. If much blood 
be present in the food, the feces may be almost black, owing to the 
formation of haematin. Huckleberries and red wine likewise pro- 
duce a blackish color, chocolate and cocoa a gray; preparations of 
iron, manganese, and bismuth color the feces dark brown or black, 
owing to the formation of the sulphides of these metals: the green 
color of calomel stools was formerly supposed to be due to the 
formation of a sulphide, but is more likely caused by the pres- 
ence of biliverdin. Santonin, rheum, and senna produce a yellow 
color. 



THE FECES. 183 

Macroscopic Constituents. 

Alimentary Detritus. Upon further examination of the feces 
it is possible to find visible to the naked eye undigested particles of 
food, which are partly indigestible and partly digestible, such as 
stones of cherries, grape-seeds, woody vegetable fibre, the skins of 
berries, large pieces of connective 1 issue, undigested pieces of apple, 
pear, potato, grains of corn, etc. The latter are found in abundance 
when the food is insufficiently masticated or taken in excessive 
amounts. 

Flakes of casein, recognizable with the naked eye, are also fre- 
quently seen. Care should be taken, however, not to confound these 
with particles of stool composed of fatty acid crystals. This mis- 
take is often made, and cau readily be avoided by a microscopic 
examination. 

Foreign Bodies. In children, the insane, cases of hysteria, and 
even in people who are otherwise possessed of their normal senses, 
the physician must be prepared to find at times all kinds of foreign 
bodies, such as pins, coins, buttons, false teeth, tooth-plates with 
ragged edges, and even dirk-knives, all of which have been known 
to pass through the alimentary canal with perfect safety; certainly 
a wonderful fact, when it is remembered that so small and innocent- 
looking an object as a grape-seed may, at times, prove the cause of 
death. It must not be forgotten, however, that in certain cases of 
hysteria bodies may be shown by patients which they claim have 
passed by the rectum, but which have been wilfully added to the 
stools, such as snakes, frogs, etc. 

Microscopic Constituents. 

Constituents derived from Food. Microscopically indigestible 
and undigested constituents of food may be seen (Fig. 38), such as 
the framework of vegetable material, sometimes still containing 
starch-granules or remnants of chlorophyll; muscle-fibres, usually 
colored yellow and more or less altered in structure; elastic-tissue 
fibres are readily recognized by their double contour and bold out- 
lines. Connective-tissue fibres of the white fibrous variety can also 
generally be distinguished; when present in large quantities, how- 
ever, they are usually indicative of some digestive derangement, 
unless they be observed following the ingestion of a meal particu- 
larly rich in meat. Flakes of casein are also frequently seen. 



184 



CLINICAL DIAGNOSIS. 



Muscle-fibres are found in every stool whenever meat has been 
eaten. Under normal conditions, however, they are not numerous, 
unless particularly large quantities have been ingested. Their 
appearance under the microscope may vary considerably. On the 
one hand, fibres are met with which still retain their characteristic 
features; others are split up either partially or entirely into the 
well-known disks; but more common than both are more or less 
roundish, yellow, apparently homogeneous fragments, which at first 
sight do not resemble muscle-fibres in the least. Upon closer in- 
vestigation, however, their true nature will become apparent. It 
will then be seen that two of the sides in some portions at least are 
more or less parallel, and if the specimen be examined with an oil- 
immersion lens some traces of cross-striation can probably always 
be discovered. 

Fig. 38. 

"A 




Collective view of the feces. (Eye-piece ni., objective 8 a, Reichert.) a, muscle-fibres ; 
fe, connective tissne; c, epithelium: d, white blood- corpuscles; e, spiral cells;/, i, various 
vegetable cells ; k. triple phosphate crystals in a mass of various micro-organisms ; I, diatoms, 
(v. Jaesch.) 



Isolated starch-granules are scarcely ever found under normal 
conditions, excepting in young children who have been fed with 
much starchy material. Starch-granules enclosed in vegetable 
cells are likewise not found as a general rule, but are more com- 
mon than the isolated granules. The presence of either in large 
numbers is usually indicative of the existence of some pathologic 
condition affecting the gastro-intestinal tract. Their presence is 
easily recognized by treating microscopic preparations with a solu- 
tion of iodo-potassic iodide (Lugol's solution), when the granules 
or fragments will assume a blue color. 

The presence of fat in the feces is quite constant, even in health. 



THE FE( ES. 185 

It may occur in the form of needle-like crystals, as Fat-droplets, or 
as polygonal masses which are highly refractive and often colored 
yellow or a yellowish-red. Their true nature is easily recognized 
by adding a drop of concentrated sulphuric acid and heating, when 

they will be transformed into the characteristic fat-droplets. 

Morphologic Elements derived from the Alimentary Canal. 

1. Epithelial cells. Well-preserved cylindrical or goblet cells are 
only exceptionally found in the feces, while transition forms from 
the normal cell to mere spindles, in which a nucleus can no longer 
be recognized, are quite constantly observed. These degenerative 
changes, according to Nothnagel, are the result of an abstraction of 
water from the cells, which may alter their appearance to an extent 
that only the experienced eye is capable of recognizing their true 
character. Pavement epithelial cells, when present, are derived 
from the anal orifice. 

2. Leucocytes are almost always absent in normal stools or present 
only in very small numbers. 

3. Red blood-corpuscles in very small numbers are occasionally 
observed under apparently normal conditions, but are then of no 
significance. 

4. In every stool a large number of structureless granules may 
be seen, lying either by themselves or collected into heaps; they are 
designated as detritus. 

Crystals. Xeedle-like crystals of free fatty acids, and the calcium 
and magnesium salts of the higher members of this group, occurring 
either single or arranged in sheaves, may be found in every stool. 
(Fig. 39.) They are of no significance, unless present in very 
large numbers. Nothnagel speaks of the frequent occurrence of 
certain calcium salts (of fatty acids, as he believes) in normal as 
well as pathologic stools. He states that they are almost always 
bile-stained and occur in irregular, sometimes eliptical, oval, or 
circular masses, in which a crystalline structure cannot be distin- 
guished. They are apparently of no importance. Quite common, 
also, are crystals of neutral calcium phosphate and ammonio-magne- 
sium phosphate, the former occurring in the form of more or less 
well-defined wedge-shaped crystals, collected into rosettes, the latter 
presenting the well-known coffin-shape when the stool is mushy, 
while in firm stools irregular fragments are mostly found. At one 



186 



CLINICAL DIAGNOSIS. 



time the arnmonio-magnesium phosphate crystals were supposed to 
be characteristic of typhoid stools, but it is now known that they 
occur in normal feces, as well as under the most varied pathologic 
conditions. Their presence is of no diagnostic significance. It is 
important to note that the neutral phosphates are never stained by 
bile-pigment, and the triple phosphates only in rare instances. Both 
are easily soluble in acetic acid. Crystals of oxalate of calcium 
may be found in abundance following the ingestion of certain 
vegetables, such as sorrel and spinach. They are usually found 
imbedded in the vegetable debris. They are readily recognized by 
their characteristic envelope-form, their insolubility in acetic acid, 
and their solubility in hydrochloric acid. Not infrequently they 
are bile-stained. 



Fig. 






Fatty crystals obtained from the feces. 



Lactate of calcium is frequently seen in stools of children receiv- 
ing a milk-diet, occurring in the form of sheaves composed of radi- 
ating needles. Calcium carbonate is rarely observed, but occasion- 
ally occurs in the form of amorphous granules or dumb-bell shaped 
crystals. Calcium sulphate crystals are likewise rare, but may be 
produced artificially by the addition of sulphuric acid, when beau- 
tiful needles and platelets may be observed. Cholesterin, while 
always present in solution, is rarely observed in crystalline form. 
(Fig. 40.) The writer found it only twice in several hundred ex- 
aminations. Hsematoidin crystals are never found in normal stools. 
Charcot-Leyden crystals occur principally under pathologic condi- 



THE FECES. 187 

tions, and, according to the writer's experience, arc never found in 
normal stools. 

Parasites. The parasites which occur in normal feces may be 
divided into vegetable and animal parasites. 

VEGETABLE Parasites. These are always present in enormous 
numbers. What relation they bear to the process of digestion is 
as yet an open question. The idea held by Pasteur and many 
others, that animal life cannot go on in the absence of bacteria 
from the digestive tract has recently been disproved by Nuttall 
and Tierf elder. A guinea-pig removed by Csesarean section from 
the uterus of the mother-animal under antiseptic precautions was 
placed in a sterilized glass cage and nourished for a week with 
sterilized food. The air which the animal breathed was likewise 
sterilized. During this week the animal consumed about 330 c.c. 
of milk and appeared to be normal in every respect. At the expi- 
ration of the week it was killed, when a microscopic examination 
of the intestinal contents revealed the entire absence of bacteria. 
Culture-experiments were likewise negative. 

Macfayden, Neucki, and Sieber likewise found that their now so 
often quoted fistula patient continued in good health, and even 
gained flesh, although the entire large intestine, in which bacterial 
activity is always greatest, was thrown out entirely for a period of 
many weeks. 

Fungi. Fungi, with the exception, perhaps, of the oidium albi- 
cans, which has at times been observed, are but rarely found in the 
feces. 

Schizomycetes. Saccharomyces cerevisise belongs to the normal 
constituents, as it were, of the feces, and is found in its character- 
istic forms, three or four buds, however, being but ordinarily 
observed. Owing to the glycogen present in their substance, they 
assume a mahogany color when treated with a solution of iodo- 
potassic iodide. They should not be confounded with a class of 
bacteria which closely resemble the saccharomyces in appearance, 
but are colored blue when treated in the same manner (see below). 

Bacteria. The bacteria are the micro-organisms yjizlzoyr^ which 
are found in the feces. Their number is truly enormous. Sucks- 
dorif thus found in his own person that on an average 53, 124,000,000 
were eliminated in the twenty-four hours under normal conditions. 
About 97 per cent, of these are directly derived from the ingested 
food, and the remaining 3 per cent, from swallowed saliva. If we 



188 CLINICAL DIAGNOSIS. 

recall the strongly bactericidal power of the gastric juice, such an 
observation must at first sight appear most surprising. It should 
be remembered, however, that the spores of the bacteria are far less 
susceptible to the action of the hydrochloric acid, and that large 
amounts of the ingesta are carried into the small intestine at a time 
already when hydrochloric acid has not as yet appeared in the free 
state. 

On the whole, the bacteriologic flora of the intestinal contents is 
fairly constant, but, as in the other cavities and channels of the 
body where bacteria are invariably met with, transient guests are 
also not uncommon. The majority of the bacteria which are here 
encountered are, as a general rule, harmless, but it is important to 
note that under suitable conditions a number of these may develop 
pathogenic properties. Roughly speaking, the bacteria which may 
be normally found in the feces can be divided into two classes. 
Those belonging to the first order are stained a yellow or a yel- 
lowish-brown with iodo-potassic iodide, while those belonging to 
the second class are colored blue or violet by the same reagent. 
To the former belong the bacterium termo, the bacillus subtilis, 
and a large number of micrococci, into a description of which, 
however, it is not necessary to enter at this place. Under the 
second heading v. Jaksch describes the following forms: 

1. Micrococci occurring in the zoogloea stage, which are colored 
a violet-red. 

2. Short, thin rods, tapering slightly at both ends, and in their 
microscopic appearance much resembling the bacillus of the septi- 
caemia of mice; sometimes they contain one or two little bodies, 
which are not stained by the reagent. 

3. Short or long rods, which resemble the leptothrix buccalis in 
their behavior toward iodo-potassic iodide. 

4. Bacilli resembling the bacillus subtilis. 

5. Bacillus butyricus. This micro-organism, according to Brieger, 
is the cause of butyric-acid fermentation. It occurs in the form of 
broad rods with rounded-off extremities, but may also be elliptical 
or spindle-shaped. With LugoFs solution it is colored blue or 
violet either entirely or only in its central portion. 

6. Large round forms, characterized, when unstained, by a pale 
lustre, and which very much resemble yeast-cells (see above). 

7. Micrococci, which assume a reddish, but not very pronounced 
tint. 



THE FECES. 189 

It should be mentioned that this second class of micro-organisms 
is not so largely represented in the feces as the first. 

To speak more specifically, the following bacteria have thus Par 
been isolated from the feces : bacillus coli communis, bacterium 
laetis aerogenes, bacillus subtilis, proteus vulgaris, bacillus putri- 
ficus coli, bacillus liquefaciens ilei, bacterium ilei, bacterium ovale 
ilei, bacillus gracili ilei, the veil bacillus of Escherich, bacillus 
butyricus, bacillus Utpadel; streptococcus coli gracilis, streptococcus 
coli brevis, streptococcus liquefaciens ilei, streptococcus pyogenes 
duodenalis, staphylococcus liquefaciens albus, staphylococcus lique- 
faciens flavus, micrococcus ovalis, the porcelain-coccus of Escherich, 
tetradencoccus. In addition various other bacteria have been found, 
but have not as yet been obtained in pure culture. This is especi- 
ally true of certain forms of spirillum. 

The specific pathogenic bacteria which may be found in the feces 
as well as those above mentioned, which may at times develop patho- 
genic properties, will be described in detail later on. 

Animal parasites are probably never present under strictly nor- 
mal conditions. 

Chemistry of Normal Feces. 

Reaction. The reaction of the feces is usually alkaline, some- 
times neutral, rarely acid, the alkalinity being due to ammoniacal 
fermentation, the acidity to lactic- and butyric-acid fermentation 
taking place in the intestines. In infants the stools are normally 
acid. 

General Composition. The following table, taken from Gau- 
tier, will give an idea of the composition of fresh feces, calculated 
for 1000 parts by weight: 

Water 

Solids 

Total organic material . 
Total mineral material . 
Alimentary residue 

The organic material yielded: 

Aqueous extract 
Alcoholic extract . 
Ethereal extract 

1 Including 54 parts of mucin, epithelium, and calcareous suits. 

- Not comprising earthy phosphates. 3 Of this, 3.2 cholesterin. 



Adult man. 


Suckling 


733 00 


851.3 


267.00 


148.7 


208.75 


137 l 1 


10.95 2 


13.6 


83 00 




53.40 




41.65 


8.20 


30.70 


17.6 8 



190 CLINICAL DIAGNOSIS. 

la addition, there are gases, which vary considerably in amount 
according to the nature of the food ingested, such articles as beans, 
heavy bread, potatoes, etc., increasing their amount very consider- 
ably. 





Milk diet. 


Meat diet. 


Vegetable diet 




Per cent. 


Per cent. 


Per cent. 


Carbon dioxide 


. 9-16 


8-13 


21-34 


Hydrogen . 


. 43-54 


0.7-3 


1.5-4 


Marsh gas . 


. 0.09 


26-37 


44-55 


Nitrogen . 


. 36-38 


45-64 


10-19 



Of these gases, C0 2 is referable to alcoholic and butyric-acid 
fermentation, as well as to albuminous putrefaction, taking place 
in the intestines. Marsh gas, CH 4 , is similarly formed during 
the fermentation of cellulose, while the nitrogen has been partly 
swallowed and is partly referable to albuminous putrefaction. A 
portion also is probably derived from the blood, and it may 
be mentioned in this connection that the enormous quantities of 
C0 2 so often discharged in cases of hysteria are undoubtedly 
attributable to this source, the gas passing from the blood through 
the gastro-intestinal mucous membrane into the stomach and in- 
testines. 

In order to give a general idea of the chemical constituents of the 
feces these may be divided into: 

1. Food-material, which could be assimilated, but which was 
taken in excess, such as starches, fats, and a small amount of non- 
assimilated albuminous material. 

2. Indigestible substances, such as chlorophyll, gums, pectic pro- 
ducts, resins, various coloring-matters, nuclein, chitin, and insoluble 
salts, viz., silicates, sulphates, earthy phosphates, ammonio-magne- 
sium phosphate, etc. 

3. Products derived from the digestive canal, as mucus, partly 
transformed biliary acids, dyslysin, cholesterin, lecithin. 

4. Substances in process of absorption, as emulsified fats, fatty 
acids, leucin, and biliary acids. 

5. Products of decomposition, referable to microbic activity; fatty 
acids, comprising the entire series from acetic to palmitic acid, the 
latter being especially abundant; butyric and iso-butyric acid, lactic 
acid, phenol, cresol, indol, skatol, excretin, amido-acids, and acid- 
amides, leucin and tyrosin, phenyl-proprionic, phenyl-acetic, hydro- 
paracumaric, and parahydroxylphenyl-acetic acid, ammonium car- 
bonate and ammonium sulphide. 



THE FECES. 191 

(J. Products of metabolism eliminated through the intestines: 
area, uric acid, and xanthin bases. 

7. Pigments: steroobilin, lnematin, hydrobilirubin, coloring-mat- 
ters derived from the blood, and, in abnormal conditions, bile- 
pigments. 

8. Water. 

9. Gases, as 0O 2 , CH 4 , H, and N. 

The study of these substances as a whole, as well as in detail, is 
of considerable importance, not only from the standpoint of the 
physiologist, but also from that of the clinician, giving, together 
with a careful urinary analysis, the clearest idea of the metabolic 
processes taking place in the body. 

The chemical study of the feces has so far not received the atten- 
tion which it deserves, and data of but little practical importance 
have been obtained from the work accomplished. This field will, 
without doubt, furnish highly important results in the course of 
time, those gained in the microscopy of the feces being certainly of 
a nature to encourage a detailed chemical study also. Up to the 
beginning of the eighties the morphologic and bacteriologic study 
of the feces had been similarly neglected, but brilliant results have 
been achieved within the last few years. It is only necessary to 
recall the discovery of the cholera bacillus by Koch in 1884; of 
the amoeba coli by Losch and Kartulis, and its relation to tropical 
dysentery; the relation of bothriocephalus latus and anchylostoma 
duodenale to certain forms of severe anaemia; not to speak of the 
generally recognized importance which the examination of the feces 
for the eggs of parasites in general has assumed within late years. 

It is impossible to give here a detailed description of the various 
chemical constituents which have been mentioned. Only the most 
important ones and those especially interesting from a physiologic 
and pathologic standpoint will be considered. 

Phenol, Indol, and Skatol. Tyrosin, produced during the pro- 
cess of albuminous putrefaction, and also during tryptic digestion, 
must be regarded as the mother-substance of phenol, cresol, indol, 
and skatol. It may be represented by the formula : 



/ 



CH 2 — (NH 2 )— COOH 



C 6 H ' = C 9 H n XO s . 

The relation which phenol, cresol, indol, and skatol bear to tyro- 
sin may be seen from the following formulae: 



192 CLINICAL DIAGNOSIS. 

CH 3 

I 
C 

/% 

C 6 H 4 CH = C 9 H 9 N (Skatol). 

CH 

C 6 H 4 CH = C S H 7 N (Indol). 

NH 

C 6 H 4 .CH 3 .OH = C v H 8 (Cresol). 
C 6 H 5 .OH = C 6 H 6 (Phenol). 

As the tyrosin, however, is very readily decomposed, it is usually 
not found in the feces, but the products of its decomposition instead, 
viz., the phenols, indol, and skatol. 

As will be seen more especially in the chapter on Urine, these 
bodies, after having undergone oxidation, unite with sulphuric acid, 
or, if this be not present in sufficient amount, with glycuronic acid, 
and are excreted as phenol, indoxyl, and skatoxyl sulphates or gly- 
curonates in the urine. In the feces, on the other hand, phenol, 
cresol, indol, and skatol are found as such. From these they may 
be obtained in the following manner: 

The feces are diluted with water, acidified with phosphoric acid, 
and distilled. The volatile fatty acids present, together with phenol, 
indol, and skatol, pass over. The distillate is then neutralized with 
sodium carbonate and again distilled. During this process phenol, 
indol, and skatol pass over, the fatty acids remaining behind as 
sodium salts. In order to separate the phenol from indol and 
skatol the distillate is alkalinized with potassium hydrate and 
again distilled. The phenol now remains behind, and may be 
obtained in pure form by distilling with sulphuric acid; in this 
final distillate its presence may be demonstrated by the following 
reactions : 

1. With perchloride of iron phenol yields an amethyst-blue color. 

2. With bromine-water a crystalline precipitate of tribromophenol 
results. 

3. Treated with Millon's reagent — i. e., the acid nitrate of mer- 
cury — a red color develops. 

Indol and skatol, on the other hand, pass over after treating the 
above mixture of the three with potassium hydrate and distilling. 



THE FECES. 



193 



These two bodies may then be separated from each other by taking 
advantage of their different degrees of solubility in water. 

Tndol forms small plates, melting at 52° C, which are easily 
soluble in hot water, alcohol, and ether; its odor is feculent. 

Reactions of indol: 1. When treated with nitric acid and a little 
sodium nitrite a crystalline red precipitate of the nitrate of nitroso- 
indol is obtained. 2. A small piece of pine-wood, moistened with 
an alcoholic solution of indol, acidified with hydrochloric acid, is 
colored a cherry-red. 

Skatol also crystallizes in plates, which melt at 95° C. They are 
soluble with more difficulty in water than indol, and emit a feculent 
odor. 

Reactions of skatol: 1. With nitric acid and sodium nitrite only 
a milky cloudiness results. 2. Pure skatol does not yield any color 
with pine- wood moistened with hydrochloric acid; but if a bit of 
the wood be saturated with a dilate alcoholic solution of skatol and 
then immersed in strong hydrochloric acid, it assumes a cherry-red 
and later a bluish-violet color. 3. With nitric acid of a specific 
gravity of 1.2 it gives upon boiling a marked xanthoproteic reac- 
tion — i. e., a yellow color which turns to orange upon adding an 
excess of ammonia. 

Finally, the determination of cresol in the presence of phenol, 
together with which it is obtained, is, when only small quantities 
of these substances are present, a difficult matter. They may be 
separated from each other by transforming both into their sulpho- 
acids, the barium salt of parasulphophenol being practically insol- 
uble in barium hydrate. 

Fatty Acids. The fatty acids present in the feces, as well as 
the relation existing between these, are given in the table below. 
The formula C n H 2ll +iCOOH or C n H 2 a0 2 expresses their general 
structure: 



Formic acid 


H.COOH .... 


. C H 2 2 


Acetic ' ' 


CH 3 COOH . 


. C 2 H,0, 


Proprionic acid Cri 3 CH 2 .COOH 


. C 3 H 6 2 


Butyric " 


CH 3 .(CH 2 ),.COOH . 


. C 4 H 8 2 


Isobutyric " 


(CH 3 ) 2 .CH.COOH . 


. C 4 H 8 G 2 


Valerianic " 


CH 3 .iCH 2 ) 3 . COOH . 


• C 5 H 10 O 2 


Caproic ' ' 


CH 3 .(CH 2 ) 4 . COOH . 


. c 6 n, 2 o. 


Capric " 


CH 3 .(CH,) 8 .COOH . 


• ^io 'i^(M> 


Palmitic " 


CH 3 .(CH, n (()()H . 


• Ci 6 H 8S 2 


Stearic " 


CH 3 .(CH 2 ) I6 .COOH . 

13 


• ('lM H 36°2 



194 CLINICAL DIAGNOSIS. 

These acids are derived partly from fats, partly from carbohy- 
drates, and to some extent also from proteids. 

Separation of the fatty acids from the feces: If the distillate, 
neutralized with sodium carbonate, referred to in the above method 
(p. 192), be again distilled, the sodium salts of the fatty acids re- 
main behind, the process taking place being one of sapoiiiheation : 

_ : =H:. COOH — XaX0 3 = 2C 13 H 31 COO.Na — H-0 — C 

The solution is then evaporated to dryness on a water-bath, the 
residue extracted with alcohol, the alcohol evaporated, and the hnal 
residue dissolved in water. This solution may now be further ex- 
amined. In order to separate the different fatty acids from each 
other it is best, if the quantity be sufficiently large, to transform 
them into their silver or barium salts, and to separate these by 
their varying degrees of solubility in water or by fractional distil- 
lation. 

General properties of the fatty acids : They are all monobasic, 
soluble in water, alcohol, and ether. Their alkaline salts are 
readily soluble in water and alcohol, but insoluble in ether. The 
silver salts are dissolved with difficulty. 

1. Formic acid is a colorless liquid, of a penetrating odor, boiling 
at 100' C. A concentrated solution of its alkaline salts is precipi- 
tated by AgNO a j the silver salt becomes black on standing, and 
reduction takes place at once upon the application of heat. Treated 
with perchloride of iron in a neutral solution it yields a blood-red 
color, which disappears upon boiling, while a rust-colored precipitate 
is formed at the same time. 

2. Acetic acid is a liquid of a pungent odor, which boils at 
119° C. Upon neutralization a blood-red color is obtained on the 
addition of perchloride of iron. Xeutral solutions of its salts with 
alkalies yield a precipitate with nitrate of silver, soluble in hot 
water, without reduction taking place. 

3. Proprionic acid is an oily fluid, boiling at 11 7 ~ C. With 
perchloride of iron no red color results: with silver nitrate it be- 
haves like formic acid. 

4. Butvric acid is an oily liquid, boiling at 137' C, which has 
an odor similar to rancid butter. Its salts, when treated with an 
acid, give off the characteristic odor- with perchloride of iron it 
vields no red color: with AgNO a its alkaline salts form a crystal- 
line precipitate insoluble in cold water. 




THE FECES. 195 

5. Valerianic acid boils at 176.3° C, and has a penetrating, 
disagreeable odor. Its silver salt crystallizes in plates, which are 
soluble with difficulty. 

Cholesterin. Cholesterin (C a6 H 44 0) occurs in small amounts in 
almost all animal fluids. It is also found in various tissues of the 
body, especially in the brain. Its origin and mode of formation in 
the various organs of the body, as well as the cause of its presence 
in the alimentary canal, are as yet unknown. It crystallizes in 
colorless, transparent plates, the margins and angles of which 
usually present a ragged appearance (Fig. 40). It is soluble in 
water, dilute acids, and alkalies. In boiling alcohol it is readily 
soluble, crystallizing out from this solution on cooling; it is like- 
wise very soluble in ether, chloroform, and benzol. 

In order to obtain cholesterin from the feces, in which it is 
always present, though rarely in crystalline form, the fatty acids, 
phenols, indol, and skatol must first be distilled off, as described, 
when the residue is strongly acidified with sulphuric acid, extracted 
with alcohol, and then with ether. The ethereal extract is filtered, 
the ether distilled off, and the residue digested with carbonate of 
sodium, in order to transform any fatty acids which may still be 

• Fig. 40. 




Cholesterin crystals. 

present into their salts. This mixture is then evaporated to dry- 
ness, and again extracted with ether. The alcoholic extract above 
mentioned is also filtered, supersaturated with sodium carbonate, 
the alcohol distilled off, the residue dissolved in water, and likewise 
extracted with ether. In the watery alkaline residue there remain 
bile acids, oleic, palmitic, and stearic acids, which can be separated 



196 CLINICAL DIAGNOSIS. 

by transforming them into their barium salts. The cholesterin and 
fats pass over into the ether. This is distilled off and the residue 
treated with an alcoholic solution of potassium hydrate. The alco- 
hol is evaporated on a water-bath, the remaining liquid diluted with 
water, and again extracted with ether. The fats remain in the 
aqueous solution as soaps, while the cholesterin has passed over 
into the ether. 

Tests for cholesterin: 1. Under the microscope add a drop of 
concentrated sulphuric acid to some of the crystals; they gradually 
disappear, the edges assuming a yellowish-red color. 

2. Dissolve a few crystals in chloroform, add concentrated sul- 
phuric acid, and shake the mixture : the chloroform assumes a 
blood-red to a purplish-red color, while the sulphuric acid at the 
same time shows marked fluorescence. 

The solution of soaps obtained above is acidified with dilute sul- 
phuric acid, when the fatty acids, which have separated out, may 
be filtered off and identified individually by their boiling-points 
and the analysis of their barium salts. 

The filtrate finally obtained, when neutralized with ammonium 
hydrate, contains glycerine. 

The Biliary Acids. The biliary acids found in the feces are : 
Glycocholic acid (C 26 H 43 !N"0 6 ), taurocholic acid (CogH^NSO-), and 
cholalic acid (0 24 H 4 O 3 ). 

The two former occur normally in the bile, and can be decomposed 
into cholalic acid and glycocoll and cholalic acid and taurin respec- 
tively; as this process of decomposition takes place ordinarily in the 
intestines, the third acid — i. e., cholalic acid — is always found in tne 
feces. 

In order to demonstrate the biliary acids, the fatty acids, phenols, 
indol, and skatol are first removed by distillation with phosphoric 
acid. The residue is taken up with water and boiled, and the 
filtered liquid precipitated with acetate of lead and a little ammo- 
nium hydrate. The biliary salts of lead are contained in the pre- 
cipitate, from which they can be removed by washing with water 
and finally boiling the precipitate with alcohol. The washings are 
then filtered and the lead salts transformed into sodium salts by 
treating the filtrate with sodium carbonate. After further filtration 
the filtrate is evaporated to dryness and the residue extracted with 
hot alcohol. Upon evaporating this the salts of the acids sometimes 
crystallize out as such, while more often a dirty amorphous precipi- 



THE FECES. 197 

tate is obtained, which may be rendered crystalline by treating with 
ether. The amorphous residue, however, can be employed for 
making the necessary tests: 

Pettenkofer'a test: A. small amount of the substance is dissolved 
iu water, and two-thirds of its volume of concentrated sulphuric 
acid added, care being taken that the temperature does not exceed 
00° or 70° C. A 10 per cent, solution of cane-sugar is added, drop 
by drop, stirring constantly. If biliary acids be present, the solu- 
tion assumes a beautiful red color, which upon standing turns a 
bluish-violet. Tin's test depends upon the action of furfurol, derived 
from the sulphuric acid and cane-sugar, upon the biliary acids. 

Pigments. Among the pigments present in normal feces ster- 
cobilin and hydrobilirubin must be considered. 

Stercobilin is spoken of by Gautier as the principal coloring-matter 
of the feces, derived from bilirubin by a process of reduction. Owing 
to its great similarity to hydrobilirubin it has even been said to be 
identical with this. It has been obtained by extracting the feces 
with acidulated alcohol ; this extract is diluted with water and 
shaken with chloroform, which latter dissolves the pigment. 

The difference between stercobilin and hydrobilirubin appears to 
be a spectroscopic one, the spectrum of the former, when treated 
with chloride of zinc aud ammonium hydrate, giving rise to four 
bands of absorption, while only three are obtained with the latter. 
The pronounced green fluorescence, however, is common to both. 

By means of the spectroscope it is also possible to distinguish 
between normal urobilin aud stercobilin; the latter is possibly iden- 
tical with the pathologic urobilin observed in febrile urines. 

Hydrobilirubin is identical with the urobilin of Jaffe and the 
febrile urobilin of MacMunn, and shows, as has just been mentioned, 
three bands of absorption. Its chemical formula is C S2 H 40 N 4 O 7 . 
According to v. Jaksch, it is obtained in the same manner as ster- 
cobilin. 

PATHOLOGY OP THE FECES. 

General Characteristics. 

Number of Stools. As has been pointed out (p. 181), one or 
two stools a day may be considered as normal; but here, as else_ 
where, the proverb, " Oue man's food, another man's poison," 
holds good. Having definitely determined in a given case the 



198 CLINICAL DIAGNOSIS. 

number of stools in the twenty-four hours in health, it is possible 
to state whether the particular case may be considered as normal 
in this respect — i. e., whether diarrhoea or constipation exists. 

As the consistence of the stools is altered in diarrhcea, this condi- 
tion may be denned as one in which too frequent and liquid passages 
exist, while the reverse may be said to hold good for constipation, 
the consistence of the stools in this condition being usually also 
altered. 

The term obstruction, on the other hand, denotes a state of affairs 
in which no stools are voided. In a general way it may be said 
that whatever causes give rise to increased peristalsis likewise pro- 
duce diarrhoea, and that whatever causes diminish peristalsis give 
rise to constipation. In the former condition the number of stools 
may vary from one to thirty, forty, or even fifty in the twenty-four 
hours, as in Asiatic cholera. The consistence of the stool when 
only one is passed in the twenty-four hours will, of coarse, decide 
the question whether the case should be regarded as one of diar- 
rhoea or not. One stool passed in the twenty-four hours may 
under certain conditions be regarded as a symptom of constipation, 
but more commonly this term is applied to a condition in which a 
stool occurs only every two, three, four or more days, or even 
weeks or months. 

Consistence and Form. The consistence of the stools may 
undergo variations, which run a course parallel to their number. 
They may be thin, mushy, and even watery, which latter condition 
is met with most commonly in cholera Asiatica and dysentery, but 
may also occur in any severe enteritis. 

In constipation, on the other hand, owing to an increased absorp- 
tion of water, the feces may be passed as very hard and perfectly 
dry, roundish, scybalous masses, the rotundity of which is undoubt- 
edly referable to their long sojourn in the haustra of the colon. 
The individual scybala usually vary in size from that of a hazelnut 
to that of a walnut, and are frecjuently provided with one or two 
indentations which represent impressions of the tsenise of the colon. 
Still smaller masses, closely resembling the dejecta of sheep, may 
also be seen. Their presence was formerly regarded as charac- 
teristic of stricture of the colon, but they are likewise found in 
ordinary cases of chronic constipation. Fecal ribbons and columns 
of the diameter of a pencil are found in cases of enterospasm as 
well as in stricture of the colon. 



I'll i<: FECES. 199 

Amount. The absolute amount of feces voided in the twenty- 
four hours hears an inverse relation to the Dumber of stools and 
their consistence, providing, of course, that no abnormally large 
ingestion of food has occurred, in which case an abnormally large 
stool of moderate firmness may be passed. Two exceptions must, 
however, be noted to this rule — I. e., the passage of large quantities 
of firm feces following an attack of constipation of long duration or 
an attack of severe obstruction. 

Odor. As the normal offensive odor of the feces is largely due 
to products of intestinal putrefaction, an increase in offensiveness 
will naturally be referable to conditions in which the putrefactive 
processes are increased. A most disagreeable odor is thus met with 
in the so-called acholic stools. The odor of fatty acids is observed 
in the lighter grades of infantile diarrhoea, while a markedly putrid 
odor is associated with its severer forms. A very characteristic 
odor is further noted in the stools of cholera and dysentery, owing 
to the presence of considerable quantities of cadaverin. A truly 
rotten stench is present in the gangrenous form of dysentery, and in 
carcinomatous and syphilitic ulcerations of the rectum. An ammo- 
niacal odor is due to an admixture of urine undergoing ammoniacal 
decomposition. 

Reaction. The reaction of the stool is so variable under patho- 
logic conditions that it is really of no diagnostic importance. In 
typhoid fever, it is true, an alkaline reaction is so constantly met 
with that this symptom could possibly be of some value in doubtful 
cases. Unfortunately, however, it may also be neutral, amphoteric, 
and even acid. In acute infantile diarrhoea an acid reaction is the 
rule, but exceptions are also not infrequent. 

Color. The color of pathologic feces may vary a great deal. 
When unaltered bile is present, the stools may assume a golden- 
yellow, a greenish-yellow, or even a green color. In cases of biliary 
obstruction or suppression, on the other hand, they become pasty 
and have a grayish or even a white color. This, however, is not 
so much due to the absence of coloring-matter derived from the bile 
as to an insufficient absorption of fats, as was shown by Striimpell, 
who succeeded in obtaining stools of a light-brown color after feed- 
ing patients affected with catarrhal jaundice upon a diet containing 
a minimum amount of fat. Such acholic or colorless stools, as it 
would be better to say, are not only found associated with biliary 
obstruction, however, but may also occur when the ducts are patent. 



200 CLINICAL DIAGNOSIS. 

They have thus been observed in various cases of leukaemia, carci- 
noma of the stomach or intestine, in simple infantile enteritis, 
chronic nephritis, chlorosis, scarlatina, tubercular enteritis, and 
especially frequently in debilitated consumptives and in cases of 
chronic tubercular peritonitis of children. In some of these con- 
ditions, as in tuberculosis of the intestines and of the peritoneum, 
the lack of color is probably due to a diminished absorption of fats, 
as above. In others, however, this explanation does not hold good, 
as abnormally large amounts of fat are not necessarily present. In 
such cases the lack of color is probably referable to the formation 
of colorless decomposition-products of bilirubin, such as the leuko- 
urobilin of ISTencki, but as yet nothing definite is known of the 
conditions which favor the formation of these products. In this 
connection it may be interesting to note that in those cases in which 
the biliary ducts are patent the color of the stools may vary not 
only from day to day, but even within the twenty-four hours. A 
neurasthenic patient occurring in the practice of the writer thus 
passed an acholic stool almost every morning and usually colored 
feces in the afternoon for a period of several weeks. 

Generally speaking, the color of the stools becomes lighter the 
larger the number of movements, and vice versa. In Asiatic cholera 
and dysentery they may thus be colorless, while in severe constipa- 
tion the scybalous masses may almost be black. 

If blood be present, the stools may present a scarlet-red, a dirty 
brownish-red, a coffee, or even a perfectly black color. Adherent 
blood, usually bright red in color and found on scybalous masses, 
is probably always derived from the rectum or anus, while a change 
in color, indicating an earlier date of the bleeding, usually points to 
the colon. 

An intimate admixture of blood with the stool, the color of the 
former being at the same time altered, so as to vary from a 
brownish-red to black (owing to the presence of sulphide of iron), 
is indicative of hemorrhage into the stomach or the small intes- 
tine. The darker the color of the blood the more remote from 
the anus will be, as a rule, the seat of the hemorrhage. Black 
or coffee-colored stools are thus observed in cases of ulcer of the 
stomach or of the duodenum, in nielsena neonatorum, and similar 
conditions. 

When profuse intestinal hemorrhages take place, however, as in 
some cases of typhoid fever and rnelsena, and particularly when 



THE FECES. 201 

diarrhoea exists at the same time, the blood which appears in the 
stools may be changed but very little or not at all. 

While, as a rule, simple Inspection or a microscopic examination 

of the feces will determine whether or not blood be present, it may 
at times be necessary to resort to more delicate tests, as the hemor- 
rhage may have been so slight as to escape detection with the naked 
eye or, at the same time, so far removed from the anus that blood 
shadows even cannot be found with the microscope. Hemorrhages 
of such trivial extent have been reported by Hasslin as occurring 
quite frequently in cases of chlorosis. This statement, however, 
the writer has not been able to confirm. If an investigation in this 
direction is to be made, the method of Midler and Weber (see p. 
170), or that of Korczynski and Jaworski should be employed. 

Korczyxski and Jaworski's Test. A small amount of the 
fecal material is treated with a pinch of potassium chlorate and a 
drop of concentrated hydrochloric acid. The mixture is carefully 
heated until it has become decolorized, more hydrochloric acid being 
added if necessary. The chlorine is then driven off, when one or 
two drops of a dilute solution of potassium ferrocyanide are added. 
In the presence of blood coloring-matter a distinctly blue color is 
obtained, owing to the formation of Prussian blue. 

An admixture of pus with the feces in notable amounts also gives 
rise to a characteristic color, as is seen in cases of dysentery, syph- 
ilitic and carcinomatous ulceration of the colon and rectum, follow- 
ing the perforation of a parametritic or periproctitic abscess into the 
rectum, etc. 

Green stools are observed especially in infants, and may be refer- 
able to two different causes, being dependent on the one hand upon 
the presence of a bacillus, described by Le Sage, which produces a 
green coloring-matter, while on the other it may be referable to 
biliverdin. When green stools occur frequently this condition is 
associated with the clinical symptoms of a severe cholera infantum. 

Quite characteristic also are the ipecacuanha stools, which closely 
resemble the so-called acholic stools. The green color produced 
by calomel, the yellow by santonin, rheum, and senna, the black by 
iron, manganese, and bismuth, have already been mentioned (see 
p. 182). 

Macroscopic Constituents. 

Alimentary Constituents. After having thus considered the 
number of stools, their consistence, reaction, odor, and color, it is 



202 CLINICAL DIAGNOSIS. 

now necessary to look for gross admixtures, and especially for the 
presence of undigested food-material, such as pieces of meat, flakes 
of caseiu — this especially in the stools of children — and fragments 
of amylaceous food. The occurrence of such a condition, consti- 
tuting what was formerly known as lientery, is always indicative of 
disturbed intestinal or gastric digestion, or both. It is, hence, 
observed in cases of chronic intestinal catarrh, febrile dyspepsia, 
following the use of cathartics, etc. 

Occasionally also a condition of affairs is seen in which almost 
unaltered food in large amounts is found in the feces, owing to 
a direct communication between the stomach and the colon, as in 
cases of perforating ulcer or carcinoma of the stomach. 

"When fat is present in abnormally large amounts it can usually 
be recognized with the naked eye. To this condition the term 
steatorrhea has been applied. In typical cases the fat is seen in 
the form of whitish or grayish masses, varying in size from that of 
a pea to that of a walnut, which are more or less intimately mixed 
with the fecal material, and may at first sight be mistaken for 
flakes of casein. From these it may be distinguished, however, 
by its chemical reactions and its peculiarly glistening appearance. 
In other cases stools may be seen in which the fecal column is 
covered, to a greater or less extent, with a grayish, dense, asbestos- 
like substance, while the core itself presents the usual color. Noth- 
nagel states that this appearance is referable to the congealment of 
the fat when it is exposed to a lower temperature than that of the 
body. The writer, however, has repeatedly observed this appear- 
ance in stools which had just been voided. The passage of liquid 
oil in the absence of fecal material has also been recorded, but it 
seems doubtful to the writer that the oil in such cases entered the 
body by the mouth. Following the use of oil enemata such stools 
may, of course, be seen. 

The elimination of abnormally large quantities of fat may be due 
to the ingestion of correspondingly large amounts. More fre- 
quently, however, it is referable to distinct pathologic conditions. 
A steatorrhea will thus naturally occur when an insufficient supply 
of bile is poured into the small intestine, and is hence constantly 
observed in cases of biliary obstruction. In these cases, however, 
the microscope is usually necessary to demonstrate the presence of 
the abnormally large quantities of fat. True steatorrhoea, on the 
other hand, viz., the presence of fat recognizable with the naked 



THE FECEs. 203 

eye, is more commonly met with in diseases affecting the resorptive 

power of the small intestine, such as extensive atrophy or amyloid 
degeneration of the intestinal mucosa, tubercular ulceration, etc., 
or in diseases involving the integrity of the lymphatic glands and 
vessels of the mesentery, as in chronic tubercular peritonitis, caseous 
degeneration of the mesenteric glands, etc. In simple catarrhal 
condition-, however, steatorrhea may also occur, and not only in 
infants, but, according to the writer's experience, also in adults. 
The question whether or not steatorrhea is constantly observed in 
cases of pancreatic disease, as some observers have claimed, may 
now be answered in the negative, although it must be admitted 
that the two conditions are very frequently associated. Le Nobel, 
who has recently investigated this subject, arrived at the conclusion 
that the steatorrhea in itself is of little practical importance, but 
that its association with the absence of products of putrefaction 
from the stools, the absence of the salts of the fatty acids, and the 
presence of maltose in the urine, may possibly be regarded as indi- 
cating the existence of pancreatic disease. 

Mucus and Mucous Cylinders. As long as mucus occurs in 
small particles only adherent to otherwise normal feces it is of no 
pathologic significance. Larger amounts are almost always indica- 
tive of a catarrhal condition of the colon or rectum, no matter 
whether the stool be otherwise normal or whether diarrhea exist 
at the time. Peculiar formations are occasionally seen, viz., so-called 
mucous cylinders, which are passed in large or small fragments in a 
condition which has been described by Nothnagel as enteritis rnem- 
branosa, or colica mucosa. Such masses, which at times measure a 
foot or more in length, are ribbon- or net-shaped, and are frequently 
passed in the absence of fecal matter, with severe tenesmus. They 
closely resemble Curschmann's spirals, bat lack the central thread 
and Charcot-Leyden crystals. They are probably indicative of 
chronic constipation associated with catarrh of the colon. Not to 
be confounded with this condition is the passage of masses of mucus 
which do not present the cylindrical form, but which also may be 
passed with a great deal of tenesmus and in the absence of fecal 
matter, in cases of nephroptosis, associated with gastroptosis and 
enteroptosis. These are, in all probability, also referable to a 
catarrhal condition of the colon. In cholera Asiatica particles of 
mucus are seen which resemble grains of rice, the presence of 



204 CLINICAL DIAGNOSIS. 

which was formerly regarded as characteristic of the disease; they 
occur, however, also in ordinary catarrhal conditions. 

Biliary and Intestinal Concretions. Most important from a 
diagnostic standpoint is the examination of the feces for the pres- 
ence of biliary concretions, which should never be neglected in cases 
of colicky abdominal pain of doubtful origin, whether associated 
with jaundice or not. 

When searching for gallstones the feces should be digested with 
water and passed through a fine sieve. Biliary concretions may 
then be found as small, crumbling masses or as hard stones present- 
ing an irregular contour or the smooth, characteristic facets. In 
size they may vary from that of a millet-seed to that of a pigeon's 
egg; large stones are but rarely passed by the bowel unless perfo- 
ration has occurred into the intestines and usually into the colon. 

Fig. 41. 




Gallstones. 
a, cholesterin ; b, pigment-stones. 

Some calculi consist almost entirely of cholesterin, while others 
are composed essentially of inspissated bile, and still others of cal- 
careous salts. The former are the most common, and are readily 
recognized by their softness and color, which may be white, grayish, 
bluish, or greenish. Their specific gravity is lower than that of 
water. Very frequently they contain a nucleus, composed of 
earthy sulphates or phosphates. An analysis by the author of a 
large stone of this kind, weighing 10.548 grammes, gave the fol- 
lowing results: 

Cholesterin 72.59 per cent. 

Mineral salts 0.247 " 

Fats 5.09 

Biliary pigments 13.93 " 

Organic matter 7.27 " 

Calculi, which consist largely of biliary pigments, are brown in 
color. They are hard, and heavier than water. Frequently they 
contain traces of copper and zinc. (Fig. 41.) 



THE FECES, 205 

Calculi composed of calcareous salts generally present an irregu- 
lar, roughened contour. 

Within recent years Welch observed the presence of pure colonics 

of the bacillus coli communis in gallstones, apparently forming 
their nuclei. 

Analysis of Gallstones. The stone is finely powdered and 
dried at a temperature of 100° C. It is then extracted with boiling 
water and the washings concentrated upon a water-bath to about 
100 c.c. One portion of this amount is evaporated to dryness, and 
the soluble residue, as well as the mineral ash, determined after 
desiccation at a temperature of 105° C. The other portion is like- 
wise evaporated to dryness and extracted with alcohol containing a 
small amount of ether, sodium glycocholate being thus obtained. 
After treatment with hot water, as described, the substance is 
successively extracted with alcohol and ether. In the alcoholic 
extract fats and a small amount of cholesterin will be found. The 
greater portion of the latter is contained in the ethereal extract. 
The residue, which is insoluble in hot water, alcohol, and ether, is 
treated with a moderately strong solution of hydrochloric acid, the 
earthy phosphates and oxides being thus obtained united to pig- 
ments. The bilirubin is removed from the latter by extracting 
with boiling chloroform. The pigments which are not dissolved 
in this manner are biliprasin, bilihumin, etc. 

Intestinal concretions (enteroliths) are rare and usually come from 
the appendix. At times they contain some foreign body, such as a 
grape-seed, as a nucleus, upon which calcium and magnesium salts 
have become deposited. 

Fecal calculi or coproliths are likewise only rarely found in the 
feces. They represent inspissated fecal material which has become 
impregnated with lime and magnesium salts. More commonly they 
are found at the post-mortem table in the caecum, in the haustra of 
the colon, and in the rectum. 

Microscopic Examination. 

Attention should be directed to the presence of eggs of parasites, 
protozoa, certain pathogenic bacteria, remnants of food, blood-cor- 
puscles, epithelial cells, pus-corpuscles, and mucus. 

Technique. In hospital work the stool should be passed into a 
well-warmed bed-pan and examined at once. This is particularly 



1 6 - AL DIA OJfOSLS. 

important in the search for amoeba?. In private practice patients 
should be instructed to send their stools to the physician at once, 
when saspicious-looking particles should be placed upon the warm- 
stage or examined upon a well-warmed slide. A very convenient 
form of warm-stage, which may be obtained from instrument- 
makers at low cost, is composed of brass and made to be held in 
position on the stage of the microscope by spring clips. It is 
about 3 cm. long and 3 cm. broad, and has cemented to a recessed 
bottom an ordinary glass slip; an opening of 1.35 cm. is in the 
centre of the stage. To one of the long sides of the brass stage is 
fitted a projecting stem, about 10 cm. long, to which the heat of a 
spirit-lamp is applied. 

For ordinary purposes it is well to place the stool, if watery, in a 
conical glass and to cover it with a layer of ether, so as to diminish 
the disagreeable odor. If mushy or firm, it should be spread out 
upon a plate and covered with a layer of turpentine, or a 5 per 
cent, solution of carbolic acid or thymol. 

Remnants of Food. It has already been pointed out that 

:::»us microscopic remnants of food are observed in normal feces. 
Ed pathologic conditions it is necessary to determine whether or not 
such remnants be present in abnormal amount, presupposing, of 
course, that excessive quantities of food have not been ingested. 
It is often possible to draw definite conclusions as to the state of 
intestinal digestion from the excess of one form of non-digested 
material over another. The presence of large quantities of undi- 
gested starch may be regarded as indicating a serious catarrhal con- 
dition of the small intestine. It may, indeed, be said that the occur- 
rence of more than mere traces of this material should always be 
regarded with suspicion. An increase in the number of muscle- 
fibres will likewise be observed under the same conditions. 

The so-called acholic stools are usually very rich in fat, and par- 
ticularly so in cases of biliary obstruction associated with jaundice. 
At other times, however, the lack of color, as has been mentioned 
above, is not referable to the secretion of an insufficient amount of 
bile, but to the presence of colorless decomposition-products of bili- 
rubin, such as the leukourobilin of Nencki. In these cases abnor- 
mally large quantities of fat are not always present. The conclu- 
sion that a stool contains excessive amounts of fat because it is 
apparently acholic is hence not justifiable unless a microscopic ex- 



THE /'/ 207 

Epithelium. Epithelial cells, when present in large numbers, 

always indicate an inflammatory condition of sonic portion of the 
intestinal tract. 

Cylindrical epithelial cells are found in abundance in all inflam- 
matory conditions affecting the intestinal mucosa. They are almost 
exclusively seen imbedded in mucus, and it is interesting to note 
that the cloudy appearance of the latter is referable to the presence 
of these elements and not to leucocytes, as is the case in the sputum. 
When bile-stained specimens are met with the conclusion is justifi- 
able that the small intestine is involved. Degenerative forms are 
mostly seen; well-preserved cylindrical or goblet cells may, how- 
ever, also be found, and are, according to the writer's experience, 
very much more common than under normal conditions. 

Epithelioid cells are sometimes found in cases of carcinoma of the 
rectum. 

Red Blood-corpuscles. Unaltered red blood-corpuscles, accord- 
ing to Xothnagel, are but rarely observed in the feces, no matter 
how intensely red they may be colored, provided that an ulcerative 
process affecting the colon or the rectum can be excluded, in which 
case large numbers may be observed, as, for example, in the severer 
forms of dysentery. If the hemorrhage has occurred higher up in 
the intestine, large and small masses of brownish -red color are seen, 
which consist of haematoidin, instead of red blood-corpuscles. They 
are mostly amorphous, but in the same or other specimens the char- 
acteristic rhombic crystals of haematoidin may be observed. In 
general it may be said that the higher the seat of the hemorrhage 
the darker will be the color of the pigment and the less the chances 
of finding well-defined red corpuscles. In such cases recourse must 
be had to the haemin- (p. 40) or the iron- test of Korczynski and 
Jaworski (p. 201). 

Mucus. Small hyaline particles of mucus, visible only with the 
microscope, are not infrequently met with under pathologic condi- 
tions, and are of distinct diagnostic significance. When bile-stained 
their presence is always indicative of disease of the small intestine 
proper, while colorless particles point to a catarrhal condition of 
the upper portion of the large intestine or the lower portion of the 
small intestine. Beginners should be careful not to mistake appar- 
ently hyaline particles of vegetable residue for mucus. The latter 
never yields a blue color when treated with iodine or iodine and 
sulphuric acid, and examination with a high power will show the 



208 CLINICAL DIAGNOSIS. 

entire absence of any definite structure. Both forms, viz., colorless 
and colored particles, are found intimately mixed with the feces, 
and may be very abundant. In addition to these forms Nothnagel 
has described the occasional occurrence of large numbers of roundish 
or irregular, very pale hyaline or opaque formations, which are 
entirely devoid of structure. Some specimens are homogeneous, 
while others present a distinctly rimous appearance. They have 
thus far only been found in liquid stools, and are apparently of no 
diagnostic importance. To judge from their optic behavior they 
probably consist of mucus. 

Leucocytes. The presence of a large number of leucocytes usu- 
ally indicates a severe catarrhal, if not an ulcerative, condition of the 
intestines, the number of leucocytes or pus-corpuscles standing in a 
direct relation to the intensity of the inflammatory process. Pure 
pus in large amounts is observed especially in dysentery and in 
cases in which accumulations of pus have perforated into the gut 
from adjacent organs or cavities. (See also p. 201.) 

Crystals. The crystals which may occur in the feces have 
already been briefly considered (p. 185). Of these the so-called 
Charcot-Leyden crystals deserve more detailed consideration. 
While occurring at times in normal stools, as also in those of 
typhoid fever, dysentery, and phthisis, such observations are rare. 
They appear to be quite constantly present, on the other hand, in 
cases of anchylostomiasis and anguilluliasis. They are also fre- 
quently associated with ascaris lumbricoides, oxyuris, taenia solium 
and saginata. In cases of trichocephalus they are seen but rarely, 
while they are always absent in the case of taenia nana. These 
observations, made by Leichtenstern, are very important, and, 
according to the same observer, the occurrence of Charcot-Leyden 
crystals should always excite suspicion as to the existence of helmin- 
thiasis and lead to a careful examination of the feces for parasites 
or their ova. Their persistence in the feces after the evacuation of 
what would appear to be a complete taenia should be regarded as 
indicating the non-removal of the head. In a case of amoebic 
colitis, occurring in the practice of Dr. Lewis, of Baltimore, these 
crystals were also observed in fairly large numbers. 



THE l't-:' 7 209 

Amm \i Pab LSI i i>. 



I. — Protozoa : 

Rhizopoda, 
Monera, 

Amoebina, Amoeba coli. 
Flagellata b. mastigophora, 
Monadina, 

Cenomonadina, Cerconionas. 
Isomastigoda, 

Tetramitina, Trichomonas, 
Polymastigina, Megastoma entericum. 
Infusoria ciliata s. vera, 

Ilolotricha, Balantidium coli. 
Gregarina s. sporozoa, 
Coccidia. 

II. — Vermes : 

Platodes, 
Cestodes, 

Taenia saginata. 
Taenia solium. 
Taenia nana. 
Taenia diminuta. 
Taenia cucumerina. 
Bothriocephalus latus. 
Krabbea grand is. 
Trematodes, 

Distoma hepaticum. 
Distoma lanceolatum. 
Distoma Buskii. 
Distoma sibiricum. 
Distoma spatulatum. 
Distoma conjunctum. 
Distoma heterophyes. 
Amphistoma hominis. 
Distoma haematobium. 
Distoma pulmonale. 
Annelides, 

Nematodes, 
Ascarides, 

Ascaris lumbricoides. 

Ascaris rnystax. 

Ascaris maritima. 

Oxyuris vermicularis. 
Strongyloides, 

Anchylostomum duodenale. 
Trichotrachelides, 

Trichocephalus hominis. 

Trichina spiralis. 
Khabdonema strongyloides, 

Anguillula intestinalis. 
14 



210 CLINICAL DIAGNOSIS. 

III. — Insecta : 

Piophila casei, 
Drosophila melanogastra. 
Homialomyia. 
Hyodrothoea meteorica. 
Cystoneura stabulans. 
Calliphora erythrocephala- 
Palleuria rudis. 
Lucilia caesar. 
Lucilia regina. 
Sarcophaga hsematoides. 
Eristalis arbustorum. 
Anthomyia. 

Protozoa. The rhizopoda are essentially characterized by the 
fact that locomotion does not take place by the aid of independent 
organs, but by means of pseadopodia, viz., protoplasmic processes 
which the animal is capable of protruding from any portion of its 
body. Six orders have been described by zoologists, but only one, 
possibly two, have thus far been found in the feces. 

Whether or not representatives of the monera occur in the feces 
of man is still an open question. If so, they are apparently of no 
pathologic significance. 

Of the amcebina, on the other hand, a most important member 
has been found, viz., the amoeba coli, Losch. 

The history of the discovery of this parasite and its relation to 
those severe forms of tropical dysentery and liver-abscess which are 
met with even in our more temperate zones is of much interest, and 
at the same time illustrates the great importance which attaches to 
a systematic examination of the feces in all aggravated forms of 
diarrhoea. 

In 1875 Losch discovered, in the stools of dysenteric patients, 
actively moving, cell-like bodies of a roundish, pear-shape, oval or 
irregular form. He did not regard these as the cause of the dis- 
ease, however, but looked upon them as being only accidentally 
present. Similar bodies have been observed in Hong-Kong by Nor- 
mand in cases of colitis; and also by v. Jaksch. Sansino found 
them in a case in Cairo, and Koch in East Indian dysentery. It 
is interesting to note that Koch was the first to suspect the exist- 
ence of a definite relation between dysentery and these organisms. 
Cunningham claims to have found amoebae frequently in the stools 
of cholera patients at Calcutta, and Grassi in normal stools, but 
especially abundant in cases of chronic diarrhoea. Whether all 



THE FECES. 



211 



these observations are correct, and whether the organisms observed 

were identical in all eases, is, of course, difficult to say. So much 
is certain, that the subject was still a very unsettled one when Kar- 
tulis announced " that dysentery and tropical liver-abscess associ- 
ated with dysentery are caused by the presence of the amoeba coli," 
basing his conclusion upon an examination of 500 cases. The fact 
that this parasite was absent in all other intestinal diseases, such as 
typhoid fever, intestinal tuberculosis, the ordinary forms of diar- 
rhoea, etc., speaks most strongly in favor of Kartulis' view. 

In perfect accord with these observations were those made at the 
Johns Hopkins Hospital by Osier, Lafluer, and Councilman. Osier 
was the iirst in this country to demonstrate the presence of the 
amoeba coli in a case of liver-abscess, both in the pus of the abscess 
and in the stools. Stengel, Musser, Dock, and others confirmed 
these observations, so that the pathogenic character of the amoeba 



Fig. 42. 




The amoeba coli. 



coli may now be regarded as an established fact. This statement 
is based not only upon the few facts, more historical in character 
than otherwise, which have just been detailed, but rather upon the 
ensemble of collected data, among which the absence of micro- 
organisms other than the amoeba in the pus of the liver-abscesses, 
and the constant presence of the latter in such cases, rank among 
the most important. 

The size of the amoeba? varies from 10 p. to 20 <i. When at rest 
their outline is, as a rule, circular, occasionally ovoid; but when in 



212 CLINICAL DIAGNOSIS. 

motion they present the extremely irregular contour of moving 
amoeboid bodies (Fig. 42). The protoplasm can be differentiated 
into a translucent, homogeneous ectosarc or mobile portion, and a 
granular endosare, containing the nucleus, vacuoles, and granules. 
"Within the endosare the vacuoles constitute the most striking feat- 
ure. Sometimes the interior seems to be made up of a series of 
closely set clear vesicles of pretty uniform size. As a rule, one or 
two larger vacuoles are present, the edges of which are not infre- 
quently surrounded by fine dark granules. True contractile vesicles 
displaying rhythmic pulsations have not been observed, although 
the vacuoles at times may be seen to undergo changes in size. In 
some the nucleus is quite distinct, while in others it may be alto- 
gether invisible. 

Most distinctive are the movements of these bodies. From any 
part of the surface a rounded, hemispherical knob will project, and 
with a rapid movement the process extends and the granules in the 
interior flow toward it. In these movements the clear ectosarc 
seems to play the most important part. 

In this connection the author wishes to refer to the occurrence of 
Laveran's plasmodium malarice enclosed in red corpuscles, in the 
stools of cases of malarial colitis. In one case of chronic malarial 
intoxication with dysenteric symptoms the diagnosis was first made 
after an examination of the stools for amoebae, which, however, 
were absent, while a number of plasmodia could be demonstrated, 
pointing out the probable nature of the colitis. 

The flagettaJba s. mastigophora differ from the rhizopoda in being 
provided with from one to eight flagella which serve as organs of 
locomotion and possibly also for the apprehension of food-particles. 
Representatives of two orders only, viz. . monadina and isomastigoda, 
have been found in the feces. Of the monadina in turn only one 
family, viz.. cenomonadina. and of the isomastigoda only two fami- 
lies, viz., tetramitina and polynia stigma, are represented. 

The cenomonadina are small, oval, frequently elongated bodies. 
provided with one long flagellum at the anterior end, at the base 
of which food vacuoles are situated. At the posterior end amoeboid 
movements may be observed, and there can be no doubt that the 
taking up of food, to some extent at least, also occurs by the aid of 
pseudopodia. To this family belongs the cercomonas of Davaine 
and Lambl. The tetramitina are small, elongated bodies, provided 
with four flagella and a lateral, undulating membrane, which was 



THE FECES. 



213 



formerly mistaken for a posteriorly directed flagellum. The tail 
end of the organism tapers to a point. The nucleus is located at 
the base of the flagella. To this family belongs the parasite which 
was first discovered by Donne in the vagina, and which was later 

also found in the feces and variously designated as trichomonas 
hominis, ccrcomonas coli hominis, etc. 

The polymasUgina are small, somewhat oval bodies, provided 
with two or three flagella, situated either anteriorly or laterally— 
two or three on each side— while at the same time two additional 
flagella issue from the posterior end, which may either be rounded 
of/ or taper to a point. To this family belongs the megastoma 
eutericum of Grassi. 



Fig. 43. 




Cercomonas intestinalis. 
a cercomonas of Davaine, after Leuckart ; b, cercomonas intestinalis, after Lambl ; c, d, 
same, ordinary forms; ej, same, well-developed forms; g, h, i, same, degeneration-forms; 
jfc, I, same, abortive forms. 

Only three parasites belonging to the order of the flagellata have 
thus far been encountered in the human feces, viz., the cercomonas 
hominis of Davaine and Lambl, the trichomonas of Donne, and the 
megastoma entericum of Grassi. To judge from the earlier litera- 
ture upon the subject, many others have also been found, but more 
modern investigations have shown that these are in reality identical 
with the three just mentioned. The question whether or not these 
flagellate bodies are of pathologic importance still remains subjudicc. 
Thev are apparently only met with in diseases associated with diar- 



214 



CLINICAL DIAGNOSIS. 



rhcea, and it appears that in some cases at least this is directly 
dependent upon their presence. In others the impression is gained 
as though they merely maintained an already existing diarrhoea, 
referable to other causes, while in a third class of cases no relation 
can be discovered between their presence and the disease in question. 
Cercomonas of Davaine-Lambl, syn., cercomonas hominis (Davaine); 
monas (Marchand); monas lens (Grassi); monas monomitina (Grassi). 
The adult organism (see Fig. 43) is oval or roundish in form, and 
provided anteriorly with a single long flagellum and posteriorly 
with a tail-like appendage. Its length varies from 0.005 to 0.014 
mm. The younger forms are pear- or S-shaped, and sometimes 
entirely irregular in outline; the flagellum is either absent or only 
rudimentary. 

Upon prolonged observation it will be seen that the adult para- 
site loses its flagellum and may protrude a protoplasmic process 
instead, while vacuolation occurs at the same time, indicating 
approaching death. 



Fig. 44. 




Trichomonas intestinaiis. 
a, a', c, trichomonas of the urine, after Marchand ; 6, trichomonas vaginalis, after Donne 
&', same, after Scanzoni and Kollicker ; d, trichomonas intestinaiis, after Piccardi ; e, e', e" 
same, amoeboid forms ; /,/' trichomonas of the urine, after Dock. 



Trichomonas, Donn6, syn., trichomonas vaginalis (Donne) ; tricho- 
monas hominis (Grassi); monocercomonas (Grassi); cimsenomonas 



THE FKCES. 



215 



(Grassi); protorycomyces coprioarius (Cunningham and Lewis); 
oercomonas eoli hominis (May); trichomonas intestinalis (Leuck- 
art and Roos); cercomonas s. bodo urinarius (Kiinstler). The 
parasite (Fig. 44) is oval or spindle-shaped and measures from 
0.012 to 0.030 mm. in length by 0.010 to 0.015 mm. in breadth. 
From its anterior pole four flagella are given off, which are almost 
as long as the organism itself. From this point an undulating 
membrane extends laterally to the posterior pole, which may be 
rounded off or tapers to a tail-like appendage. This membrane 
is best seen when the movements of the flagella have ceased or in 
specimens fixed in bichloride of mercury solution (1 : 5000). The 
nucleus is situated at the base of the flagella, but is usually only 
visible in stained specimens (methylene-blue). At times the organ- 
ism may be observed to assume an amoeboid form; the movements 
of the flagella have then ceased, and psendopodia-like processes 
are protruded. The parasite is identical with the trichomonas 
which has been found in the vagina and in the urine. 



Fig. 45. 




Megastoma entericum. 
a, b, V, c, d, &', &", various forms of cercomonas intestinalis, after Lambl ; d, d', encysted 
forms of megastoma entericum, after Grassi and Schewiakoff; e, megastoma entericum, adult 
form. 



216 CLINICAL DIAGNOSIS. 

Megastoma enter icum, Grassi, syn., cercomonas intestinalis (Lambl); 
megastoma intestinale (Biitschli); lamblia intestinalis (Blanchard); 
dimorphus muris (Grassi). The parasite (Fig. 45) is pear-shaped, 
and measures from 0.01 to 0.021 mm. in length by 0.0075 to 0.05 
mm. in breadth. In its anterior portion a more or less well-marked 
depression can be made out, which constitutes the peristome or 
mouth opening of the organism. It is provided with eight flagella, 
grouped in pairs. The first pair originates on the sides of the peristome 
and is directed backward. The second and third pair are situated 
somewhat posteriorly and are likewise directed backward, while the 
fourth pair issues from the tapering tail-end of the body. In fresh 
specimens the eighth flagella can usually not be made out, as the 
third and fourth pair are frequently agglutinated. The best results 
are obtained when the organism has been killed with bichloride 
solution. The individual flagella vary from 0.009 to 0.014 mm. 
in length. In the anterior portion of the peristome two round, 
hyaline bodies can be recognized which represent nuclei. Vacuoles 
are absent, and nutrition occurs through osmosis, the parasite ad- 
hering to epithelial cells by its peristome. When treated with 
fixing solutions the chitinous envelope can be readily recognized. 
In the encysted form the organism is oval and measures from 0.007 
to 0.1 mm. in diameter. 

Grassi observed it in mice, rats, cats, dogs, rabbits, and sheep. 

Balantidium coli (Malmsten), syn., paramoeciurn coli. The organism 
is egg-shaped, 0.1 mm. long, and covered entirely with fine cilia, 
which are grouped most densely about the mouth, while the anus 
is surrounded by only a few. In its interior are found a nucleus, 
two contractile vesicles, and frequently fat-droplets, particles of 
starch, etc. The parasite is most common in Sweden, but has also 
been observed in Germany, Cochin-China, Italy, and the United 
States. Infection occurs through the dejecta of swine. 

The fourth class of protozoa, viz., the Gregarina or sporbzoa, is 
also said to be represented in the human feces. The coccidia and 
psorosperms belong to this order. They are small, oval bodies, 
measuring about 0.022 mm. in length, and contain in their 
interior a large number of small nuclei, arranged in groups. They 
are entirely devoid of organs of locomotion, and obtain their nutri- 
ment by endosmosis. Eeproduction occurs in a common capsule, 
which bursts at a certain time and sends forth a whole generation 
of fully developed organisms. In human pathology they have 



THE FECES. 217 

become of interest in so far as certain observers have ascribed to 
them a role in the etiology of neoplasms. A disease of the liver 
analogous to the psorospermiasis of rabbits has also been described 
in man, and parasites belonging to the same order have recently 
been observed in the skin. The two cases reported by Gilchrist 
and Rixford ended fatally, and post-mortem examination revealed 
extensive infection of the spleen, adrenal glands, testes, lymphatic 
glands, and lungs. 

Vermes. The elass vermes has interested physicians since 
time immemorial, and is referred to in the writings of Hippocrates 
and others, special mention being made of the ascarides, called lum- 
brices, and the platodes, called lati. Speaking of the former, Lucas 
Tozzi, in 1686, says: " They find their way into the heart and its 
pericardium, into the brain, the lungs, the veins, and gall-bladder, 
where they are difficult to ( catch. ' " The same author, speaking 
of their effects upon the body, enumerates the following conditions 
as caused by their presence : epilepsy, vertigo, sopors, delirium, 
convulsions, headache, syncope, palpitations, feelings of anxiety, 
cough, vomiting, nausea, diarrhoea, hiccough, prickling, borborygmus, 
erosions, tabes, acute and chronic fevers, and innumerable other 
maladies. 

It was even then deemed very important to make a diagnosis 
before the administration of an anthelmintic — a point which is 
well to bear in mind at the present day, and the eggs, segments, 
or parasites themselves should be sought for in every suspected 
case before treatment is begun. 

Tcenia saginata, Goeze, syn., t. mediocanellata (Kuchenmeister); 
t. incruris (Huber); t. dentata (Nicola). This parasite (Fig. 46) is 
now known to be the most common tapeworm both in Europe and 
Xorth America. Infection occurs through the ingestion of measly 
beef. Its length varies from 4 to 8 m. The head, which is devoid 
of a rostellum, is surrounded by four pigmented suckers, each of 
which is encircled by a dark line. The individual segments are 
quite thick and opaque, and diminish in length as the head is 
approached, the largest measuring from 2 to 3 cm. They are each 
provided with a very much branched uterus, which opens laterally, 
the primary branches numbering about twenty on each side. The 
ova are elliptical in form, of a brown color, and usually enclosed 
in a distinct vitelline membrane. Upon careful observation a 
double contour with delicate radiating striae can be discerned. 



218 



CLINICAL DIAGNOSIS. 



In the interior the embryos are seen imbedded in a brown, granular 
material. 

Thus far the cysticercus of taenia saginata has not been observed 
in the human being. 

Fig. 46. 






Taenia saginata. 
a, natural size ; b, head much enlarged ; c, ova much enlarged. 

Tcenia solium, Rudolphi. This parasite (Fig. 47) is far less com- 
mon in this country than taenia saginata, and may indeed be re- 
garded as a curiosity. In Germany, also, it is only rarely met with 
now, while formerly it was the most common tapeworm in that 
country. This change is undoubtedly owing to the fact that raw pork 



THE FECES. 



19 



is now eaten Less frequently. In Asia and Africa it is more com- 
mon. Taenia solium is usually much shorter than taenia Bagiuata, 
rarely exceeding 3.5 m. in Length. Most characteristic is the bead, 

which is provided with four pigmented suckers and a rostellum fur- 
nished with from twenty-four to twenty-six booklets, arranged in 
a double row. The mature segments measure from 1.0 to 1.5 cm. 
in length by 6 to 7 mm. in breadth, and contain a uterus which has 
only five to seven branches, thus differing greatly from that of tajnia 
saginata. The ova are round, of a brownish color, and surrounded 
with a thick, radially striated membrane; in their interior the hook- 
lets of the embryos can usually be made out. 

Fig. 47. 




Head of T. solium. X 45. (Leuckart.) 



At times, though rarely, an autoinfection with the proglottides 
of taenia solium has been observed in the human being. Under 
such conditions the embryos of the worm are set free in the stomach, 
and may then migrate into various parts of the body, where they 
become encysted, constituting the so-called cysticercus celluloses stage 
in the development of the parasite. Most commonly the cysticerci 
are found in the skin; they have, however, also been observed in 
the heart, lymphatic glands, liver, bones, tongue, spinal canal, the 
brain, and the eyes. The author had occasion to observe a case of 
this kind at the Johns Hopkins Hospital (reported by Osier). The 
patient, a laboring-man, had never worked as a butcher or a cook, 
and never had a tapeworm. The cysticercus nodules, which were 
situated between the skin and fascia, were very numerous, seventy- 
five being counted on one day. One of these nodules was removed 
for examination and shown to be referable to the cysticercus of 
taenia solium. The only subjective complaints in this case were 
pains and stiffness in the arms and legs. The individual cysticercus 
is elliptical or roundish in form, measuring from 1 to 10 mm. in 
diameter. In its interior the characteristic hooklets were seen. 



220 



CLINICAL DIAGNOSIS. 



Tcenia nana, v. Siebold, syn., hynienolepsis (Weinland). This 
parasite (Fig. 48) has not been observed in America, but seems to 
be the most common tapeworm in Italy and Egypt, being found 
especially in young people, and often causing severe nervous symp- 
toms, such as convulsions, loss of consciousness, and even melan- 
cholia. It is only 8 to 25 mm. long and 0.5 mm. broad. The 
head is ball-shaped and provided with four suckers and a rostel- 
lum, bearing twenty-four to twenty-eight hooklets arranged in a 
single row along its anterior edge. The individual segments are 
of a yellowish color and about four times as broad as long. The 
uterus is oblong and contains numerous ova, which are colorless, 

Fig. 48. 






' 



Tsenia nana. Head, with rostellum drawn in ; proglottis ; egg. (v. Jaksch.) 

oval, and surrounded by a distinct non-striated membrane. They 
measure from 0.039 to 0.060 mm. in size. In their interior the 
embryonic worm, provided with five or six hooklets, may be dis- 
tinguished. The number with which this parasite at times infests 
the digestive tract is most astonishing, 5000 and even more having 
been counted at various times. The cysticercus stage occurs in 
snails, which are frequently eaten raw in Egypt and Italy. 

Tcenia diminuta, Rudolphi, syn., tsenia flavapunctata (Weinland); 
tsenia minima (Grassi) ; taenia varerina (Parona); taenia leptocephala 
(Creplin). Taenia diminuta was first described in man by Leidy, 
Grassi, and Parona. It measures 20 to 60 mm. in length, and is 
armed with two suckers, but without a rostellum. The ova resem- 
ble those of taenia solium. The cysticercus occurs in certain cater- 
pillars and cocoons. In man it has only been found in six instances. 

Tcenia cucumerina, Bloch, syn., taenia canina (Linne); taenia ellip- 
tica (Batsch). (Fig. 49.) The parasite is almost exclusively found 



THE l-KCES. 



221 



in children, the infection occurring through dogs and oats. Lts 
length varies from 10 to 40 mm. The head is provided with 
about sixty hooklets, Burrounding a rostellum in irregular rows. 
When the latter is protruded it appears as a club-shaped protuber- 
ance. The ripe segments have a reddish color, and are very much 
longer than broad. The ova contain embryos already armed with 
hooklets. The cysticercus occurs in fleas. 



Pig. 49. 









Taenia cucuruerina. Head ; proglottis ; magnified, 
(v. Jaksch.) 



Fig. 51. 




Bothriocephalus latus. Head. 



Fig. 50. 








p«a Egg* 





Bothriocephalus latus. 



Bothriocephalus lotus, Bremser, syn., taenia lata (Linue); diboth- 
•ium latum (Rudolphi). (Figs. 50 and 51.) This worm is 5 to 



222 



CLINICAL DIAGNOSIS. 



9 m. long. Its head is shaped like a bean, and upon its flat sur- 
faces two distinct grooves can be discerned, which probably act as 
suckers. The ripe segments are almost square in form, with the 
genital apparatus opening in the median line. The uterus presents 
four to six convolutions on each side, which become especially dis- 
tinct when the segments are placed in water or exposed to the air. 
A rosette-like appearance is then obtained, which is quite charac- 
teristic. The eggs are oval, 0.07 mm. long and 0.045 mm. broad; 
they are enclosed in a brown envelope, at the anterior end of which 
a little lid can be recognized. Their contents consist of protoplasmic 
spherules, all of about the same size, which are lighter in color in 
the centre than at the periphery. The larva? have been found in 
various fishes, such as the perch, trout, and burbot, but most fre- 
quently in the pike. It is thus readily understood why the parasite 
is most common in lake regions, as in Switzerland, northern Russia, 
southern Scandinavia, and northern Italy. Outside of Europe it 
is most common in Japan. In the United States it has only been 
found in a few imported cases. From a pathologic standpoint it 
is of much interest, as it appears to stand in a genetic relation to 
certain forms of severe anaemia . 

Krabhea grandis, Blanchard. This parasite has been observed 
in only one instance — in eastern Asia. It is said to resemble 
certain bothriocephali which are found in seals. 

Trematodes. The various forms of distoma which belong to this 
order are essentially hepatic parasites, and rarely occur in the feces. 



Fig. 52. 



Fig. 53. 






Distoma hepaticum. (Leuckart.) Distoma lanceolaram (x 8) and eggs. (v. Jaksch. 



Distoma hepaticum, Abildgaard, syn., fasciola hepatica (Linne). 
(Fig. 52.) This, the most common liver-fluke, is 28 mm. long 



THE FECES. 223 

and 12 mm, broad, being formed like a leaf. The head is pro- 
vided with a sucker, and a second sucker may be found at its 
ventral surface. Between the two the genital opening is located, 
leading into a skein-shaped uterus. The edges are oval, measuring 
0.13 mm. in length and 0.08 mm. in breadth, the anterior end 
being provided with a lid; their color is brown. In the United 
States the organism is practically unknown, while in Germany it 
ifi most common in sheep. In the human being it is rare in both 
countries. Infection occurs through a small snail, the Linnaeus 
minutus, which is found, in Germany especially, upon watercress. 

Distoma lanceolatum, Mehlis, has only been found in five cases, 
all of which occurred in Germany. (Fig. 53.) It is much smaller 
than distoma hepaticum, measuring 8 to 9 mm. in length by 2 to 
3.3 mm. iu breadth. It is lancet-shaped, tapering toward the 
head end, but otherwise closely resembles the above parasite. 
The ova are 0.04 mm. long, 0.03 mm. broad, and contain fully de- 
veloped embryos. In the ruminants the organism is quite common. 

Distoma Buskii, Lancester, syn., distoma rhatonisii (Poirier); dis- 
toma cranum (Busk). The parasite has been observed in only 
three cases — in China. It is much larger than the common 
liver-fluke. Infection probably occurs through certain fishes and 
oysters. 

Distoma $i6/r/citm,Winigradoff, syn., distoma felineum (Rivolta). 
This parasite was found in Tomsk by Winigradoff in eight autop- 
sies out of 124. Its length may reach 13 mm. The ova are 0.026 
to 0.038 mm. long and 0.010 to 0.022 mm. broad. The intestines 
are simple and extend to the posterior extremity of the body. Its 
surface is smooth. 

Distoma spatulatum, Leuckart, syn., distoma endemicum (Balz); 
distoma japonicum (Blanchard); distoma sinense (Cobbold). The 
habitat of the organism is in cats. In the human being it has only 
been observed in Japan, where it appears to be quite common in 
certain localities. It is about 11.75 mm. long and 2 to 2.75 mm. 
broad. The living parasite is of a reddish color and translucent, 
so that it is possible to distinguish all its interior organs. The 
ova measure 0.028 to 0.030 mm. in length by 0.016 to 0.017 mm. 
in breadth, and are enclosed in a colorless envelope. 

Distoma conjunctum, Cobbold, distoma heterophyes, v. Siebold, and 
amphistomum hominis, Lewis and McConell, are other parasites 
which have been observed in a few isolated cases, but are as yet 



224 



CLINICAL DIAGNOSIS. 



of no special interest. The last-named appears to be common in 
elephants. 

Distoma hcematobium and dlstoma pulmonale are described in the 
sections on Blood and Sputum, respectively. 

The annelides are very common intestinal parasites, and of these 
especially the nematodes. 

Ascaris lumbricoides (Linne) (Fig. 54) is the cylindrically shaped 
worm so commonly seen in children and in the insane. The head 
consists of three projections or lips, which are provided with 



Fig. 54. 




Ascaris lumbricoides. (v. Jaksch.) 
a, worm, half natural size ; b, head, slightly magnified ; c, eggs. (Eye-piece I, objective 8 A, 

Reichert.) 



suckers and fine teeth. The male measures about 215 mm., the 
female about 400 mm. in length. The tail-end of the male is rolled 
up on its ventral surface like a hook and provided with papillae. 
The genital aperture of the female is situated directly behind the 
anterior third of the body. The eggs are yellowish-brown in 
color, almost round, and measure 0.06 mm. by 0.07 mm. in size; 
they are surrounded by an irregular albuminous envelope, which 
is covered by a tough shell; the contents are coarsely granular. 
Ascaris lumbricoides occurs all over the world, and also infests 



Tin: ri:a:s. 



225 



the pig and the OX. Its presence may occasion very severe nervous 
symptoms, but fortunately this is but rarely the ease. 

Asoaria mystax, Zeder, syn., ascaris marginata (Rudolphi); ascaris 
alata (Bellingham); (Fig. 55) is smaller and thinner than ascaris 
lnmbricoides, but otherwise very similar. The head is pointed and 
provided with wing-like projections, which constitute the main point 
of difference between the two. The male measures 45 to 60 mm. 
in length, the female 110 to 120 mm. Its ova are round, larger 
than those of ascaris lnmbricoides, and enclosed in a membrane 
which is covered with numerous small depressions. The worm is 
very common in dogs and cats, but very rare in man. 



Fig. 55. 



Fig. 56. 




Hi 




Ascaris mystax. (v. Jaksch.) 
a, male ; b, female ; c, head ; d, egg. 



Oxyuris vermicularis. (v. Jaksch.) 
a, head ; b, male ; c, female ; d, eggs. 



Ascaris maritima, Leuckart, also belongs to this class. It has 
only been observed in one case — in Greenland. 

Oxyuris vermicularis, Bremser, syn., ascaris vermicularis (Linne); 
ascaris graecorurn (Pallas). (Fig. 56.) The male is 4 mm., the 
female 10 mm. long. At the head three lip-like projections with 
lateral cuticular thickenings may be seen. The tail of the male is 
provided with six pairs of papillae, and the female with two uteri. 
The eggs are 0.05 by 0.02 to 0.03 mm. in size, and covered by a 
membrane, showing a double or triple contour; in the interior, 
which is coarsely granular, the embryos are contained. 

The female worm lives in the ciecum, but after impregnation 
travels downward to the rectum. Here it causes most annoying 

15 



226 



CLINICAL DIAGNOSIS. 



symptoms, which are especially distressing at nights, when the 
organism emerges from the anus. In doubtful cases of pruritus 
ani aut vulvae an examination of the feces should be made for this 
parasite. The ova themselves do not occur in the feces. 

Anchylostomum duodenale (Dubini); anchylostoma duodenale 
(Dubini); strongylus quadridentatus (v. Siebold); dochmius anchy- 
lostomum (Molin) ; sclerastoma duodenale (Cobbold); strongylus 
duodenalis (Schneider); dochmius duodenalis (Leuckart); un- 
cinaria duodenalis (Roilliet). (Fig. 57.) The organism belongs 

Fig. 57. 




Anchylostomum duodenale. (v. Jaksch.) 

a, male, natural size ; 6, female, natural size ; c, male, magnified ; d, female, magnified ; 

e, head (eye-piece II., objective C, Zeiss) ; /, eggs. 

to the family strongyloides, and is one of the most dangerous 
parasites met with in the human being. It has been found in 
Italy, Germany, Switzerland, Belgium, Egypt, and in the West 
Indies (Jamaica). Within the last year a few cases have also 
been reported in the United States. From a pathologic stand- 
point the parasite is of special interest, as its presence gives rise 
to severe and often fatal anaemia. Griesinger was the first to 
point out that the so-called Egyptian chlorosis is produced by this 
organism. In every case of severe anaemia, particularly when 
occurring in patients who have been working in mines, tunnels, 
and brickyards, the feces should be carefully examined for the ova 
of this parasite. The worm itself is only rarely found. Its habitat 
is in the jejunum. Infection takes place through contaminated 
drinking-water. 



THE FECES. 



227 



Fig. 58. 



The male is <> to 1 L.5 nam, long, the female 10 to 18 nun. The 
head, which tapers somewhat, Is turned toward the hack; the month 
capsule is hollowed out and surrounded by Pour teeth; the tail of 

the male forms a three-lobed bursa, while that of the female tapers 
conirallv; the genital opening is behind the middle of the body. 
Its eggs have an oval form and a smooth surface, measuring 0.05 
to 0.06 by 0.03 to 0.04 mm. In their interior two or three seg- 
menting bodies are found, which rapidly develop outside of the 
human body, so that after twenty-four to forty-eight hours embryos 
may be found in the same feces iu which the eggs were observed, or 
fully developed ova may be found after allowing the feces to stand 
for only a few hours. 

Trichocephalus hominis, Schwank, syn., trichocephalus dispar 
( lviulolphi); mastigodes (Zeder); trichuris (Biittner). This para- 
site, which belongs to the family triehotrachelides, is formed like a 
whip, the last-end being the head-end, while the tail-end is very 
much thicker. The male measures 46 mm. and the female 50 mm. 
in length. The eggs are brownish in color, measuring 0.05 by 0.06 
mm. in size, and presenting a doubly con- 
toured shell, with a depression at each end 
closed by a lid. The contents are coarsely 
granular. It is said to be the most widely 
distributed intestinal parasite, occurring in 
Europe, North America, Asia, Africa, and 
Australia. Its habitat is in the caecum. 
The living worm is only rarely found in the 
feces. 

Trichina spiralis (Owen) (Fig. 59) is 
rarely found in the feces. The male meas- 
ure- 1.5 mm. in length, and is provided 
with four papillae between the conical lips. 
The female is 3 mm. long. The uterus is 
situated nearer the head than the ovary, 
which opens into it. Fertilization occurs 

-1 • ... i i mi t i a, male, slightly magnified ; b, 

in the intestinal canal. Ihe eggs develop femalei slightly mag „i fi ed; c, 
into embrvos in the uterus, emerge from eggs (eye-piece n., objectives 

i • , ' . . . f ,. A, Reichert). 

this, and penetrate the intestinal walls, 

whence they are carried by the blood-current to the muscles. 

Trichinosis is far less common in the United States than in Europe. 

Anguillula intedinalis is 2.25 mm. long and 0.04 mm. broad; its 




Trichocephalus dispar. 

(v. Jaksch.) 



228 



CLINICAL DIA GNOSIS. 



mouth is three-cornered and bounded by three little lips. The 
genital aperture is located between the middle and posterior third 
of the body. Its eggs are similar to tb se >i anchylostomnm duod- 
enale, but longer and more elliptical, with tapering poles: they 
are never found in the feces, only the embryos occurring here. 




Trichina spiralis in muscle. The elongated shape of the cysts is due to the fact that these 
were near the insertion of the muscle into its tendon. In the lowest specimen the worm is 
dead and calcified. . axs 



When sexually mature the parasite is called angaillula stercorals : 
this again gives rise to embryos, which may in turn enter the intes- 
tinal canal. The anguillula stercoralis Fig. 60 nas a rounded 
body, which presents an indistinct cross-striation. Its head is like 
the top of a cane and :1 with two lateral jaws, each of which 

is armed with two teeth. The male measures 0.08 mm., the female 
1.22 mm. in length. The pathologic significance of this parasite 
has not as yet bee itely ascertained, but from its resemblance 

uchylostomum duodenale it has become important from a diag- 
nostic point of view. 

Insecta. As the larvae of the various insects met with in the 
feces have so far been very little studied, they will not be con-: - 
ered at this place, particularly as they do not appear to possess any 
points of clinical importance. 

Vegetable Parasite-. Among the pathogenic vegetable para- 
sites the bacillus of cholera, of typhoid fever, and of tuberculosis, as 



/•///•: FEi / v 



229 



Fig. 60. 



well as the bacilli of Booker, the bacillus coli communis, the bacillus 
lactia aerogenes, and the proteus vulgaris deserve especial consid- 
eration. 

A< early as 1848 certain " vibrios'' were observed in abundance 
in the stools of cholera patients by Yirchow, and in 1849 by Pouchot, 
Britton, and Swayne, no import- 
ance, however, being attached to 
their presence at the time. 

The first accurate and detailed 
studies of the organism found in 
cholera stools were made in 1883 
by the members of the French and 
German commissions sent to Egypt. 
to investigate the true nature of the 
dreaded disease. The results of 
their work were first published by 
Koch in his report to the Berlin 
Sanitary ( )ffice in 1883, and in 1884 
by Strauss, Roux, Xocard, and 
Thuillier. 

The clinical recognition of chol- 
era Asiatica has become a fairly 
simple matter since Pfeiffer de- 
monstrated that the blood-serum of 
cholera patients possesses the prop- 
erty of causing arrest of motility 
and the agglutination of the specific 
bacilli. Bouillon-cultures, how- 
ever, can usually not be employed, 
as particles of the film, when 
broken up, may easily be mistaken 
for agglutinated bacilli. It is best 
in every case to make use of a^ar- 
culture- sixteen to twenty-four hours old, and to prepare emulsions 
in bouillon or normal salt-solution as occasion requires. The emul- 
Bion, moreover, should always be examined microscopically before 
use, so as to insure the absence of any conglomerations of bacilli. 
The blood is then diluted in the proportion of 1 : 10 or 1 : 15. 
If the test-tube method is employed, the tubes should only be kept 
in the incubator (37° C.) for one or two hours. Upon the slide the 




Anguillula stercoralis. (Bizzozero.j 



230 CLINICAL DIAGNOSIS. 

reaction is obtained in from five to twenty minutes. If no distinct 
agglutination is observed at the end of one hour, the diagnosis of 
cholera is rendered improbable. Dried blood preserves its agglu- 
tinative properties for a considerable length of time, and may also 
be used for examination. 

The comma-bacillus is a slightly arched or even half-moon-shaped 
little rod, somewhat shorter than the tubercle-bacillus (Plate Till. , 
Fig. 1). Occasionally two are placed end to end with their convexi- 
ties in opposite directions, presenting the appearance of the letter S. 
Koch detected these bacilli in the intestinal contents and feces, 
but rarely in the vomited matter, in Asiatic cholera only. In 
the stools they at times occur in such numbers as to constitute 
pure cultures. In plate-cultures kept at a temperature of 22° C. 
white colonies with serrated borders may be observed after twenty- 
four hours. The color of such a colony is slightly yellow or rose- 
red, its central portion gradually assuming a deeper tint, and finally 
becoming liquefied. Upon agar-plates the bacilli form a grayish- 
yellow, irregular, slimy coating, but do not liquefy the culture- 
medium. In stab-cultures, after twenty-four hours a wdiitish 
color may be observed along the line of the stab; around this there 
is formed a funnel-shaped depression, which gradually increases 
in size and apparently contains a bubble of gas. The upper por- 
tion of the culture-medium at the same time becomes liquefied, 
the lower portion remaining solid for days. In a suspended drop 
spirochsetaB-like spirals are observed at the margins, which often 
present as many as twenty distinct arches. 

Upon what may be termed specific reactions in the recognition 
of the cholera-bacillus no reliance can as yet be placed, and even 
the cholera-red reaction of Brieger, obtained by treating cultures of 
the bacillus with concentrated hydrochloric acid, does not rest upon 
a sufficiently firm basis to be of much service. 

Closely related to Koch's comma-bacillus and possibly bearing 
to cholera nostras the same relation that the former bears to cholera 
Asiatica is the bacillus of Finkler and Prior, discovered in 1884 and 
1885 (PJate VIII., Fig. 2). This is, however, readily distinguished 
from the former by the following characteristics: It is larger and 
thicker than the comma-bacillus; the colonies on gelatin plate-cul- 
tures show equally round and sharp-edged forms, which present a 
granular appearance under a low or medium power, and are usually 
of a brown color. The organism liquefies gelatin very rapidly, a 



PLATE VIII. 



FIG i 






/// 






i\ii" lH4'v>% 






Spirillum of Asiatic Cholera. Impression Cover-slip from a Colony 
Thirty-four Hours Old. (Abbott.) 



FIG. 2. 



VM 



Bacillus of Finkler and Prior. (Cornil and Babes.) 



FIG. 3. 




Bacillus 



'I Typhoid Fever from a Culture Twenty-foui 
on Agar-agar. (Abbott.) 



Hours Old, 



THE FECES. 231 

penetrating, excessively fetid odor being developed at the same 
time. In stab-cultures the bacillus of cholera Asiatics forms a 
funnel-shaped depression, while the bacillus of Finkler and Prior 
forms a stocking-like depression. Further work is still necessary 
in this direction, which may not be altogether unprofitable and 
may even yield most important results. 

The typhoid bacillus, discovered by Eberth in 1880 in the abdom- 
inal organs of patients dead with typhoid fever, is, unfortunately, 
nor so readily recognized in the feces as the organisms just consid- 
ered. The main difficulty lies in its differentiation from the bacillus 
coli communis, with which it has mauy points in common. 

A few years ago Eisner reported a method which, it was claimed, 
would enable the general practitioner to make the diagnosis of typhoid 
fever in twenty-four hours, and iu the hands of some observers, such 
as Brieger, satisfactory results were obtained. Others, however, 
were less successful, and since the discovery of Widal that the 
blood-serum of typhoid patients possesses the property of arresting 
the motility of typhoid bacilli and of causing their agglutination, 
the method has practically been abandoned. His procedure was the 
following: An aqueous extract of potato (500 grammes to the liter) 
is treated with 10 per cent, of gelatin and boiled. The solution is 
then treated with 2.4 to 3.2 c.c. of a one-tenth normal solution of 
sodium hydrate in order to secure the necessary degree of acidity, 
and then filtered and sterilized. 

When needed, a portion is placed in an Erlenmeyer flask and 
treated with 1 per cent, of potassium iodide. The mixture is 
inoculated with fecal material and the necessary plates prepared. 
Upon this medium only a few species of bacteria will grow, princi- 
pally the bacillus coli and the typhoid bacillus. After twenty-fonr 
hours the bacillus coli colonies are already mature, while the typhoid 
bacillus colonies can scarcely be made out with a low power. After 
forty-eight hours, however, the latter appears as small, highly re- 
fractive, extremely fine granular colonies, closely resembling drops 
of water, which can be readily distinguished from the large, much 
more granular, brownish colonies of the bacterium coli. This dif- 
ference is brought oat particularly well if diluted plates have been pre- 
pared. 

Brieger, who carefully repeated the experiments of Eisner, states 
that typhoid bacilli are found in abundance in the stools as long as 
fever exists, but with approaching convalescence they diminish in 



-:■-." >;^ 



:: IV 



:-. z-_ 



not obtained such s atis fa c tory resold 

p. 79), which is much sin : ::: pa 

. '..t" "■■ . t . . ■ . r '. :_: : :: El^fT. Tir 

7 ^nres the typhoid badiMip 

__r~::": :i ;ir ::m :: :•: ii : : : _ _ " 
:_::■:.-:::;:«:.- : : :z '.:.:-: i- :__""::- e . . 
TDL, ¥%. a.) The ends 
:■: :,": : .:: ilr-E^f t;i_t« :_ 
i -It" ^: :~ "ri~ r-T-3 ii.~. 
:: ii-re-si. ~.:.:: -112 
— . = 1 :•■:'_ :: zl:., :::- : :: 
: ■ ^zip-ntaie of 37° 



:~.::.~zz j.i^ :_r :._~-z\r 

.. -_ - . -. - ■ 

z ' '": ill ; ~tLl: 1 =ef 
:> :!-: i_::r rrliiiL. Lis 
mizzLei!- 



■,-T 



~i~fr. 



2 : -^ :-:,:i: t- 
:„t -:.:- : : : :-■: 
■...•*. : : _irl ::: : : 



described in thechapti 

-:: : :-:- ] :: —_L;z± :_- 
. :'.r_T : r :.._::■; '. -jn- 
it liseis-r. is ::it:~. ; 



may be 

,-::L 



.i::i: Lirr: 



:: 1: -: 2. : - : :• ::.:- ::::::::: 
mneoos memhrane. 

2" :■:'<>: us :.:• ::_ :-:- i:ir :. 
infantile diarrhoea. Seven of 

:-;2 viniinl- Ii22-? "A" 
measuring from 3 p to 4 p in 
motile and liquefying. Colon 

11—-"::: :~ i :-:lir. 

2i-t : " : ■: : :: \ '.ii2. ~ 
feces, is described at this place, 



:. iis: : Tsrel :~ 

: irleZ." -Lrllrl 

:':--:::: ::.::. 

: :_1t ._:.:■; ::t: - 
: ■". .i t - : : ;.. zzzz :■. . s 

n:_::::i :: :2 T 



Z: 



Iz^: :i :i.ses :: 

.-:- zz-. : i : ill :: - 

— .- - 



:Z~ 



:..-~- -."_:•■ i 



THE FECES. 233 

that it may at times develop pathogenic properties. It has thus been 
found in the 1 pus in cast's of purulent perforating peritonitis, angio- 
cholitiSj pyelonephritis, etc., and, as indicated elsewhere, at times 
forming the nucleus of gallstones. It occurs in the form of delicate 
or coarse rods, measuring about 0.4 (i in length, which manifest a 
certain degree of motility, due to the presence of one or two polar 
flagella. The organism is stained by the usual aniline dyes, and is 
decolorized by Gram's method. The colonies upon gelatin closely 
resemble those of the bacillus of typhoid fever, forming small whitish 
specks in the gelatin, and delicate films with serrated borders upon 
the same medium, which, moreover, is not liquefied. They also 
grow upou potato. As in the case of the cholera bacillus the 
nitroso-indol reaction can be obtained when the organism is grown 
upou peptone-containing media. In solutions of glucose active 
fermentation takes place. 

The bacterium lactis aerogenes (Escherich) closely resembles the 
organism just described, and may also at times develop pathogenic 
properties. It was recently found by Heyse in a case of pneuma- 
turia. It is seen quite constantly in the stools of sucklings, but 
may also be met with in those of adults. It occurs in the form of 
rather stout rods, which frequently lie in pairs, resembling diplo- 
cocei. The organism is non-motile. Like the bacillus coli com- 
munis it is decolorized by Gram's method. In pJate-cultures it 
forms dense white films; in stab-cultures a chain of white colonies 
resembling beads is seen. In the latter, moreover, if the stab be 
closed, bubbles of gas will be seen to form, which rapidly increase 
in number and size. Milk is coagulated in large lumps in twenty- 
four hours; the formation of gas is, at the same time, much more 
intense than in the case of the bacillus coli communis. 

Proteus vulgaris, Hauser. This organism, while usually regarded 
a- non-pathogenic, should be numbered among the bacteria which 
may at times develop pathogenic properties. Baginsky and Booker 
have frequently found it in the stools in cases of infantile summer 
diarrhoea. Escherich observed it at times in the meconium. Others 
have encountered it in inflammatory conditions of exposed surfaces, 
in appendicitis, in perforative peritonitis, and even in closed abscesses, 
either alone or in association with other bacteria (Welch). A mixed 
inf.-ction of the proteus and Loffler's bacillus has also been observed. 
The organism forms little rods, measuring about 0.6 ti in diameter, 
while their length is variable; at times a more roundish form i- 



234 CLINICAL DIAGNOSIS. 

observed; at others little rods measuring from 1.25 p to 3.75 p 
in length, or even long threads. They are readily stained, but are 
easily decolorized by alcohol or Gram's method. Most character- 
istic is their growth upon nutrient gelatin. At the temperature of 
the room little depressions will be observed after six to eight hours, 
which are surrounded by a narrow zone of bacilli from which a 
thin, wide film, provided with irregular projections, extends over 
the culture-medium. From this film small islets become separated, 
which slowly wander over the gelatin and cause its liquefaction. 
The organism is motile. It decomposes urea and causes albumi- 
nous putrefaction. The nitroso-indol reaction is readily obtained in 
bouillon-cultures. 

Chemistry of the Feces. 

According to Hoppe-Seyler, mucin is a constant constituent of 
the feces, both under physiologic and pathologic conditions. Under 
normal conditions, however, it is never possible to recognize its pres- 
ence either with the naked eye or with the microscope. In order 
to demonstrate the presence of mucin in the feces they are digested 
with water and treated with an equal volume of milk of lime, the 
mixture being allowed to stand for several hours, when it is filtered 
and the filtrate tested with acetic acid. In the presence of mucin 
a cloud develops upon the addition of the acid. 

Albumin is demonstrated in the feces by treating them repeatedly 
with water slightly acidified with acetic acid. The filtrate is then 
examined for albumin according to methods given elsewhere (see 
Urine). Under normal conditions these reactions prove negative. 
Pathologically, serum-albumin has been observed in cases of 
typhoid fever and chlorosis. 

Peptones are normally absent from the feces. They have been 
observed in typhoid fever, dysentery, tuberculous ulceration, puru- 
lent peritonitis with perforation into the gut, atrophic cirrhosis, 
and carcinoma of the liver. Acholic stools are also usually rich in 
peptones. 

The peptones are demonstrated in the following manner: The 
feces are digested with water, so as to form a thin mush; they are then 
boiled, filtered while hot, and the filtrate examined for albumin, so 
as to be sure that all of this has been removed. The mucin is re- 
moved by treating with acetate of lead, when the filtrate is exam- 
ined for peptones as described in the chapter on Urine (which see). 



THE FECES. 235 

AmoDg the carbohydrates starch, glucose, and certain gums may 
be found. In order to demonstrate these the i'crv> are boiled with 
water, filtered, and evaporated to a small volume. This solution 
may now be tested with phenylhydrazin or Trommer's reagent for 
the presence of glucose (see Urine), and witli a solution of iodo- 
potassic iodide for starch (see Saliva, p. 152). The residue is ex- 
tracted with alcohol and ether, as described under the heading of 
fatty acids, and then with water. The filtrate of the aqueous ex- 
tract Is concentrated, boiled with dilute sulphuric acid, and then 
over-saturated with sodium hydrate. This mixture is treated with 
sulphate of copper and boiled in order to test for dextrin and gums. 

Bile-pigment, normally absent from the feces, occurs in large 
amounts in catarrhal conditions of the small intestine, and may be 
demonstrated by Gmelin's method, viz., a drop of the filtered liquid, 
or a particle of highly colored fecal matter, is brought into contact 
with a drop of fuming nitric acid, when the yellow color will be 
seen to pass through the various shades of the spectroscope, the 
green shade being the most characteristic. 

At times, however, it is not possible to obtain a positive reaction 
in this manner, although bile-pigment be present. In such cases 
the examination should be conducted under the microscope, and 
attention directed to bile-stained epithelial cells, leucocytes, particles 
of mucus, and crystals. 

Whenever there is increased intestinal putrefaction the fatty 
acids, phenol, indol, and skatol will, of course, be found in in- 
creased amounts. 

THE PHYSIOLOGY OF DIARRHOEA AND 
CONSTIPATION. 

Before passing on to a consideration of the condition of the stools 
in the more important diseases of the intestinal tract it may be well 
briefly to consider the most common causes of diarrhoea and consti- 
pation. 

Diarrhoea. 

Supposing normal peristalsis to result from the stimulation of the 
nervous mechanism situated in the intestinal walls — /. c, the plex- 
uses of Meissner and Auerbach — by normal chyme, it is apparent 
that an increased peristalsis indicates either that the intestinal con- 



236 CLINICAL DIAGNOSIS. 

tents possess more irritating properties, or that the irritability of 
the intestinal nervous mechanism is increased. 

Among such abnormal stimuli the following may be mentioned : 

1. Thermic stimuli. The effect of these may be said to increase or 
decrease peristalsis in the same proportion as the thermic stimulus 
differs from the normal temperature of the body. A cold injection 
thus acts more promptly than a warm one, and in many people a 
glass of cold water, taken early in the morning, before breakfast, is 
often followed by vigorous peristalsis. 

2. Mechanical stimulation. As an example of this the loose stools 
may be mentioned which follow a very large meal. A large injec- 
tion similarly acts more energetically than a small one. In such 
cases it is supposed that the increased peristalsis is referable to the 
stimulation of a larger number of nerve-endings at the same time. 

3. Chemical stimuli. These are certainly the most important and 
those which are probably responsible for most cases of diarrhoea. 
Among these must be mentioned : 

a. Certain medicinal substances belonging to the class of laxa- 
tives, drastics, cathartics, etc., some of which manifest a selective 
action for the intestinal tract, as their injection iuto a vein or 
hypodermically will also cause an increase in the peristalsis. 

b. Poisons : All the drugs of the Pharmacopoeia, with few excep- 
tions, belong to this class, as when given in poisonous doses diar- 
rhoea is produced. 

c. Poisons contained in tainted food. 

d. Poisons produced in the intestinal tract itself, referable to 
abnormally active fermentative and putrefactive processes. 

e. Certain poisons produced by specific microbes, such as those of 
typhoid fever, cholera, etc. 

4. Psychic stimuli. As an example of these the diarrhoea of the 
student before examinations may be mentioned. 

As indicated above, peristalsis will also be increased when the 
nerve-endings in the intestinal mucosa are in a condition of in- 
creased irritability. This will naturally always be the case in any 
inflammatory condition of the intestine, the abnormally filled blood- 
vessels, and at the same time an altered condition of the transudate, 
causing stimulation of the fine nerve-endings. In acute ulcerative 
conditions this state is, of course, met with in its most marked form, 
while in chronic ulcerations, where there is a gradual death of nerve- 
and muscle-substance, increased peristalsis is not so often observed, 



THE FECES. 237 

the stools, as regards consistence and number, scarcely differing 
from the normal. 

It may thus be said that whenever intestinal peristalsis through 
one of these causes has become abnormally active diarrhoea must 
result, manifested by the passage of an increased number of stools, 
which are at the same time abnormally rich in water. The increase 
in the amount of water may be due to one or two causes: first, to 
increased ingestion, aud, second, to diminished absorption. The 
first of these, however, can hardly ever be said to cause diarrhoea, 
and the latter will not result as long as resorption is undisturbed. 

The liquid stools following the administration of salts can prob- 
ably be explained by assuming a retention of water in the alimen- 
tary canal, referable to their presence. By far the most frequent 
cause of watery stools, however, following the administration of a 
drug is an abnormally active peristalsis. 

Whether in pathologic conditions associated with the destruction 
of epithelium the abnormal quantity of water observed in the stools 
can be ascribed to diminished absorption is a question which is dim- 
cult to answer, since inflammatory and ulcerative processes which, 
as has been seen, are in themselves sufficient to produce increased 
peristalsis, and hence watery stools, are taking place at the same 
time. 

On the other hand, it appears highly probable that the frequent 
aud persistent diarrhoea which occurs so constantly in cases of amy- 
loid degeneration is due to passive hyperemia in consequence of the 
degenerative changes taking place in the bloodvessel-walls, resorp- 
tion being thereby impeded. 

Remembering at the same time that the resorptive processes in 
the large intestine determine the form in which the intestinal con- 
tent- leave the body, it is readily understood that increased peristal- 
sis <>f this portion of the gut is the deciding factor in the production 
of diarrhoea, and without it an increased peristalsis alone, confined 
to the small intestine, would hardly ever be capable of causing this 
result It follows also that the more the peristalsis of the entire 
alimentary tract is increased, the more will the feces assume the 
character of the contents of the small intestine. 

Constipation. 

Hitherto the effects of increased peristalsis upon the number and 
consistence of the stools have been considered. If now peristalsis 



238 CLINICAL DIAGNOSIS. 

becomes diminished, the opposite condition— i. e., constipation — 
will result, and inversely, as in diarrhoea, this may be due to a 
diminished irritability on the part of the nervous mechanism of 
the intestinal wall. This is especially the case in the condition 
generally designated as " habitual constipation/ ; the degree of 
which will depend upon the part that the small and large intestines 
separately or together play in the process. In such cases, however, 
resorption is not increased in proportion, as might at first thought 
be imagined, and it appears to be a fairly well-established fact that 
for the carrying on of an efficient degree of resorption a certain de- 
gree of peristalsis is necessary. This is most beautifully exemplified 
in cases of cholera sicca, in which constipation exists, although the 
intestines are filled with liquid. Whether central influences play a 
part in some of the cases must as yet remain an open question. 

Different from this condition are those cases of constipation which 
are not referable to a diminished peristaltic energy, but in which, 
instead of successive contractions and relaxations, a tonic contrac- 
tion of the intestinal walls occurs. In some cases this is probably 
of central origin, as in basilar meningitis, while in others, as in lead 
colic, it may be secondary to a primary vaso-constriction along the 
intestines. It differs from ordinary constipation in the fact that 
everything that can be absorbed is here taken up. 

In atony of the intestinal muscles, finally, constipation will also 
result. This occurs, for example, after the use of cathartics, in 
peritonitis (in consequence of prolonged circulatory disturbances), 
and in alcoholics the subjects of fatty degeneration of the muscular 
walls of the intestines. 

THE FECES IN VARIOUS DISEASES OP THE 
INTESTINAL TRACT. 

Acute Intestinal Catarrh. This condition follows the ingestion 
of excessive quantities of normal food, of tainted food (meat, fish, 
cheese, etc.), beer, and of certain poisons, such as acids, alkalies, 
arsenic, corrosive sublimate, etc., when taken in toxic quantities. 
It is also observed, furthermore, as the result of a general infection, 
as in summer diarrhoea, cholera nostras, typhoid fever, and severe 
malaria, and is associated with disturbed circulatory conditions 
producing a passive hypersemia of the gastro-intestinal mucosa, 
as in diseases of the liver and portal system, in chronic heart 



77/ /•: FECES. 239 

and lung diseases, etc. How far these circulatory disturbances 
may be considered as primary causes remains to be seen. Possibly 
they merely act as predisposing causes of certain chemical processes 
taking place in the intestinal contents. 

The stools are usually increased in number in proportion to the 
degree in which the large intestine is affected. Two or three, or 
ten or more, stools may be passed within the twenty-four hours. 
In consistence they are mushy or even watery, containing in some 
cases 90 or 95 per cent. Their color is usually light yellow, but 
may, at times, be green. Microscopically, remnants of food may 
be found in large quantities, as also numerous bacteria, triple 
phosphates, isolated pus-corpuscles, and desquamated cylindrical 
epithelial cells. 

A duodenal catarrh can only be diagnosed when icterus exists at 
the same time. 

In catarrh of the jejunum and ileum, when the large intestine is 
not affected the stools are firm, formed, and speckled with small 
hyaline particles of mucus, visible only with the microscope. Usu- 
ally, however, the large intestine is also affected when the stools are 
loose and contain undigested particles of food, the latter indicating 
abnormal conditions in the small intestine. Bile-pigment is also 
met with, as only the contents of the small intestine give Gmelin's 
reaction. 

Fig. 61. 



*.•■•••• " '■.'.•" 



Rectal discharge from a case of enteritis raembranosa . 

Catarrh of the large intestine is probably always present whenever 
diarrhoea exists. 

\\ hen the colon is extensively affected mucus appears in larger 
masses than otherwise, and if the catarrh is very low down the feces 
may be formed, but are covered with mucus. 



240 CLINICAL DIAGNOSIS. 

Chronic Intestinal Catarrh. This may follow an acute attack, 
and may also occur after dysentery, severe malaria, typhoid fever, 
etc. Diarrhoea usually alternates with constipation. It is rare in 
adults, while in children it is quite frequently observed. Macro- 
scopically and microscopically it presents the same picture as in the 
acute form. 

Enteritis membranosa is a form of chronic intestinal catarrh 
characterized essentially by the evacuation of cylindrical masses 
of mucus, as described on p. 203. (Fig. 61.) 

Cholera Nostras. This is an infectious disease affecting both 
stomach and intestines, being probably dependent upon the presence 
of the bacillus of Finkler and Prior. 

The stools are first feculent, but soon become colorless and more 
and more watery, until they ultimately resemble the so-called 
rice-water stools of cholera Asiatica, and contain much serum-albu- 
min and mucin. 

Summer Diarrhoea of Infants. In this disease six or seven 
stools are passed daily, which are more liquid than normally, of a 
fetid odor, and contain flakes of casein. They are often green 
when passed, or may assume that color on standing. Mucus is 
present, and when the colon is especially affected may occur in 
sago-like particles. In severe forms pus-corpuscles, epithelial 
cells, and small amounts of blood may be present. 

Booker, in his classical work upon the summer diarrhoea of in- 
fants, arrives at the conclusion that the disease in question cannot 
be attributed to the presence of any one particular micro-organism, 
but that the " affection is the result of the activity of a number of 
varieties of bacteria, some of which belong to well-known species 
and are of ordinary occurrence and wide distribution, the most 
important being the streptococcus and proteus vulgaris. ' ' He also 
found that in the colon the bacillus lactis aerogenes occurs in greater 
number than in the normal intestine, and that it may even predomi- 
nate over the bacillus coli communis. Among other forms of bac- 
teria which occur frequently and in great abundance are small, 
short, faintly staining bacilli; long, very slender bacilli; large 
bacilli with pointed ends, and small, faintly staining spirilla. 

Dysentery. This is an infectious disease, probably caused by a 
bacillus discovered by Chantemesse and Widal. The stools during 
the first few days are irregular. A moderate diarrhoea then sets 
in, the stools being thin, but still feculent, numbering five or six 



THE FECES. 241 

per diem. After several days the diarrhoea increases and the stools 
now assume a definite character, numbering from ten to twenty or 
even fifty or sixty in the twenty-four hours. At the same time 
they become scanty in amount, usually not exceeding 10 to 15 
grammes at a time. They are now sero-sanguineous in character, 
and in them may be found smaller or larger pieces of necrotic 
tissue. Microscopically blood-corpuscles, particles of mucus, pus- 
corpuscles, and numerous bacteria are seen. According to the pre- 
ponderance of blood, pus, mucus, etc., the stools are termed sanguine- 
ous, sero-sanguineous, puriform, or mucoid, etc. Shreds of mucus, 
resembling frogs' eggs or kernels of tapioca, which are, in all prob- 
ability, casts of follicles, are also found. Typical dysenteric stools 
do not, as a rule, emit a marked odor, but in the gangrenous form 
they are very offensive. 

Amoebic Dysentery. This form of dysentery is especially in- 
teresting, not so much on account of its prevalence, however, as of 
the importance attaching to au early diagnosis, a successful treat- 
ment being altogether dependent thereupon, and differing entirely 
from that employed in the more usual forms. 

The number of stools may vary within very wide limits — from 
six to twenty or even thirty in the twenty-four hours. They may 
be wholly mucoid, streaked here and there with pus, and presenting 
a few grayish threads. Others seem to be made up of a greenish, 
pultaceous mass, in which at times large greenish, irregular sloughs 
are observed. Such stools are usually slight in amount. Occa- 
sionally large brownish, liquid evacuations are seen, in which small 
grayish-white masses occur, imbedded in blood-stained mucus. Such 
stools contain the diagnostic amoebae most abundantly. 

For a satisfactory examination of the stools the bed-pan ought 
to be well warmed and brought to the laboratory immediately for 
examination. If this be impracticable, some of the material may 
be deposited in a suitable receptacle, and the small, grayish-white 
masses placed upon a warmed slide, if a warm stage be not at 
hand. One preparation after another must now be carefully looked 
over for actively moving amoebae, or for amoeba-like bodies which 
exhibit definite movements. (For a description of these parasites 
see p. 229.) 

In addition to the amoebae other animal parasites may here be 
met with, such as the trichomonas intestinalis, which is at times 
present in very large numbers. 

16 



242 CLINICAL DIAGNOSIS. 

Red blood-corpuscles in greater or less abundance, numerous 
pus-corpuscles, more or less degenerated cylindrical epithelial cells, 
bacteria of all kinds, and even large pieces of necrotic tissue may 
also be found. 

Cholera Asiatica. In this disease the stools are very numer- 
ous, being at first feculent, but soon becoming rice-water-like. As 
large a quantity as 200 grammes may be passed at each evacuation. 
The stools are colorless, almost odorless, watery, and on standing a 
finely granular, grayish-white sediment may be seen to form at the 
bottom. The reaction is neutral or alkaline. They contain only 
0.5 per cent, of solids, a little serum -albumin, and a large amount 
of sodium chloride. In severe cases blood is present in variable 
amount. Microscopically, epithelial cells, triple phosphate crystals, 
and numerous micro-organisms are found. Of the latter the comma- 
bacillus is, of course, the most important (see p. 230.) 

Typhoid Fever. Typhoid stools are usually described as re- 
sembling pea-soup both in consistence and color. Their odor is 
usually highly offensive and characteristic. They contain a large 
amount of biliary coloring-matter and have always an alkaline reac- 
tion. Microscopically many bile-stained epithelial cells, some leu- 
cocytes, many triple phosphate crystals, and an enormous number 
of micro-organisms, especially the Clostridium butyricum of Noth- 
nagel and Eberfch's bacillus, are found. Later on they may assume 
the appearance of ulcerative stools and become almost black, owing 
to the presence of blood. 

MECONIUM. 

By meconium are meant those masses which are first excreted 
from the bowel after birth. It is a thick, tenacious, greenish-brown 
material which has accumulated during the intra-uterine life of the 
infant. Microscopically a few cylindrical ep'ithelial cells, a few 
fat-droplets, numerous cholesterin-crystals, bilirubin-crystals, and 
lanugo-hairs are found. 

Micro-organisms are absent, but soon after suckling has com- 
menced bacteria appear in abundance. The most important ones 
of those which are then constantly present are the bacillus lactis 
aerogenes, which predominates in the small intestine, and the 
bacillus coli communis, which is found more particularly in the 
large intestine. Both have already been described (see pages 232 
and 233). 



THE FECES. 



243 



In addition to these proteus vulgaris, streptococcus coli brevis, 
micrococcus ovalis, tetradencoccus, torula cerevisiae, torula rubra, 
and a few less important micro-organisms have at times been found. 

Chemically meconium contains bilirubin in considerable amount 
(recognizable by Gmelin's reaction), biliary acids, fatty acids, 
chlorides, sulphates, phosphates of the alkalies and their earths. 
It does not contain urobilin, glycogen, peptones, lactic acid, tyrosin, 
or leucin. 

An idea may be formed of its composition from the following 
table of Zweifel : 



Water 
Solids . 

Mineral matter 
Cholesterin 
Fats . 



79.8-80.5 percent. 
20 2-19.5 " 

0.978 

0.797 

0.772 



CHAPTER V. 

THE NASAL SECEETION. 

In the 'nasal secretion, which is small in amount, transparent, 
colorless, odorless, tenacious, and of a slightly saline taste, pave- 
ment-epithelium cells in large numbers, ciliated epithelial cells, as 
well as some leucocytes aud an enormous number of micro-organ- 
isms, are found. (Fig. 62.) Its reaction is alkaline. 

Fig. 62. 




Epithelial cells and mucous corpuscles found in the nasal secretion. 

In acute coryza the amount is at first diminished, but soon a 
very copious secretion occurs, which is rich in epithelial cells and 
micro-organisms. When complicated with an ulcerative condition 
pus is observed in considerable amount. 

Occasionally, in cases of traumatism, cerebral tumors, etc., cerebro- 
spinal fluid is discharged through the nose, which may be recognized 
by the fact that it is free from albumin and contains a substance 
which reduces Fehling's solution. 

Of pathogenic organisms the tubercle-bacillus and the bacillus of 
glanders may occur in ulcerative diseases of the nose, their presence 
indicating the existence of the corresponding affection. In ozsena 
a large diplococcus has been described by Lowenberg, which is 
said to be characteristic of the disease. Oidium albicaus has been 
observed in rare cases. The same may be said of the occurrence 
of ascarides and other entozoa, which at times find their way into 
the uasal passages. Charcot-Leyden crystals (which see) have been 
observed in the nasal discharge in cases of true bronchial asthma. 



CHAPTER VI. 



THE SPUTUM. 



Definition. 



Without entering into the physiology of the act of coughing, it 
may be stated in a general way that cough is the first and most 
essential factor in the elimination of irritating matter derived from 
the respiratory passages — i. e., the alveoli of the lungs, the bronchi, 
trachea, larynx, pharynx, and posterior nares. The material which 
is thus removed is spoken of as expectoration or sputum, the study 
of which forms one of the most important chapters in clinical diag- 
nosis. 

General Technique. 

The sputum should be collected in suitable receptacles, constructed 
in such a manner as to permit of their complete and easy disinfec- 
tion. The paper spit-cups (Fig. 63) which have been introduced 
within late years are admirably adapted to this purpose, as they 
may be destroyed immediately after use. 

Fig. 63. 





Sanitary spit-cup. 



When working with sputa which are known or suspected to be of 
tubercular origin, the greatest care should be exercised to keep the 
expectoration from drying and becoming disseminated in the air. 



246 CLIXICAL diag: ; SIS 

Negligence in this respect may result in the mo^ mrhms ctmne- 
quences. 

The macroscopic examination of sputa Is mast : mveniently carried 
out by placing small portions of the material upon a plate of ordi- 
nary window-glass, of suitable size, which has been painted black 
upon its lower surface, and covering the same Willi a second and 
smaller plate. If it is desired to examine individual constituents 
which have been discovered in this manner, the upper plate is slid 
off until the particle in question is uncovered, when it may be re- 
moved to a microscopic slide and examined under a higher power. 

It is also very convenient to have a portion of the laboratory 
table painted black, when unstained plates of glass may be utilized. 
If these measure about 15 by 15 cm. and 10 by 10 cm. 3 respec- 
tively, fairly large quantities of sputum may be examined w mbt 
with a low power. 

General Characteristics of the Sputa. 

The Amount. The amount of sputum expectorated in the 
twenty-four hours varies within very wide limits, depending largely 
upon the nature of the disease. Thus, only a few c.c. may be 
eliminated, or an amount reaching 600 to 1000 cc, or even more. 
Very large amounts are expectorated in cases of pulmonary hem- 
orrhage and oedema of the lun^-- - : :i_ :..- .: :: _ 
of accumulations of pus from the thoracic or abdominal cavi- 
ties into the respiratory passages; furthermore, in cases in which 
large vomica? of tubercular or gangrenous origin exist, and finally 
in cases of abscess of the lung, bronchiectasis, and even in simple 
bronchial blennorrhosa. On the other hand, the amount may be 
very small, as in incipient phthisis, acute bronchitis, and in the first 
and second stages of pneumonia. 

In private practice, as well as in hospital work, an idea should 
always be formed of the amount of sputum expectorated in the 
twenty-four hours, especially in cases in which this is abundant. 
It is apparent that a copious and long-continued expectoration 
cannot go on without exerting very detrimental effects upon the 
patient's general nutrition; in cases of pulmonary phthisis, for 
example, Renk has shown that 3.8 per cent, of all nitrogen elimi- 
nated in such cases is removed in this manner. Lanz in his recent 
experiments even found 5 per cent. 



THE SPUTUM. 247 

Consistence. The consistence of the sputum corresponds, in a 
general way at least, to its amount, and may vary from a liquid 
to a highly tenacious state. The cause of the tenacity of the 
sputum is but imperfectly understood. The mucin present does 
not appear to be the most important factor, as this has been 
observed to occur in diminished amount in pneumonic sputa, 
which are noted for their high degree of tenacity. Kossel has 
suggested that this phenomenon may be due to the presence of 
nuclei n or nuclein derivatives, while others again refer it to the 
presence of abnormal albuminous bodies of unknown character. 
However this may be, sputa are at times and not at all infre- 
quently seen where it is possible to invert the cup without losing 
a drop of its contents. This is observed especially in cases of 
acute croupous pneumonia up to the time of the crisis, providing 
that a catarrh of the bronchi does not exist at the same time. It 
is noted, furthermore, in cases of acute bronchial asthma, immedi- 
ately after an attack, and also in the initial stage of acute bronchitis. 

In cases of oedema of the lungs, on the other hand, the sputa are 
liquid and present the general characteristics of blood-serum, being 
covered, like all albuminous liquids when brought into contact with 
the air, by a frothy surface-layer. The sputa observed in cases of 
acute pulmonary gangrene, pulmonary abscess, putrid bronchitis, 
and following perforation into the lungs of an empyema or an 
accumulation of pus situated beneath the diaphragm, are fluid and 
consist of pure pus. 

Color. The color of the sputa may vary greatly. They may 
be perfectly clear and transparent, gray, yellow, green, red, brown, 
or even black. Purely mucoid expectoration is almost transparent 
and colorless, as is also the sputum of pulmonary oedema when not 
mixed with blood or pus. 

The larger the number of leucocytes the more opaque does the 
sputum become, assuming at first a white, then a yellow, and 
fiually a greenish color, the two latter colors being usually indica- 
tive of the presence of pus. Green sputa, however, may also be 
observed when bile-pigment has become admixed with the sputa, 
as in cases of perforation of a liver-abscess into the lung, for ex- 
ample. Green-colored sputa may also be observed in cases of 
jaundice, and especially in pneumonia when accompanied by icterus. 
In cases of amoebic liver-abscess with perforation into the lung the 
sputa present a color resembling anchovy sauce, which is very 



248 CLINICAL DIAGNOSIS. 

characteristic. In one case the author recognized the nature of the 
disease by simple inspection of the sputa. 1 

The inhalation of particles of carbon gives the sputum a grayish 
or even a black color; the same or an ochre-yellow or red color is 
observed in cases of siderosis. 

A red color is usually indicative of the presence of blood, the 
intensity of the shade depending upon the character of the disease. 
It is seen especially after the formation of cavities in caseous pneu- 
monia, in incipient phthisis, heart-disease, etc. In general it may 
be said that a clear, bright-red color indicates an arterial, a dark- 
red or bluish-red a venous origin of the hemorrhage. The exact 
shade will depend upon the length of time that the blood, no matter 
what its origin may be, has remained in the lungs. In pulmonary 
gangrene a dirty brownish-red color is observed, owing to the pres- 
ence of methsemoglobin, and, to some extent also, of h^matin. Quite 
characteristic is a chocolate-color, which is observed when a croupous 
pneumonia terminates in necrosis and gangrene. Equally char- 
acteristic is the rusty and prune-colored expectoration seen in cases 
of pneumonia. Occasionally a breadcrust-brown color of the sputa 
is observed in cases of gangrene and abscess of the lung, which is 
said to be quite characteristic, the color being due to the presence 
of hasmatoidin or bilirubin. 

Rust-colored, punctate, or striped sputa, moreover, are said to be 
diagnostic of brown induration of the lung. 

Odor. Most sputa are odorless. Under certain conditions, 
however, the odor may be very marked. In cases of pulmo- 
nary gangrene or putrid bronchitis the odor is of a kind never 
to be forgotten, the stench, indeed, being frightful. A somewhat 
similar, slightly sweetish odor is observed in certain cases in which 
putrefactive organisms have entered the lungs and there exerted 
their action upon the accumulated sputa, in the absence of gan- 
grene, as in cases of bronchiectasis, perforating empyema, and 
where ulcerative processes are taking place in the lungs, whether 
these be of tubercular origin or not. An odor like that of old 
cheese is occasionally observed in cases of perforating empyema; 
under such conditions tyrosin is usually found. This body, how- 
ever, has nothing to do with the odor of the sputa, both factors 
being merely indicative of certain putrefactive changes going on in 
the lungs. According to Leyden, the occurrence of tyrosin in sputa 

1 See Johns Hopkins Hospital Bulletin, November, 1890. 



THE SPUTUM. 249 

is usually indicative of the perforation of au old accumulation of 
pus into the lungs. 

Specific Gravity. The specific gravity of sputa varies within 
wide limits, mucous sputa having a specific gravity of 1.004 to 
1.008, purulent sputa one of 1.015 to 1.026, and serous sputa one 
of 1.037 or more. The determination of the specific gravity, how- 
ever, will scarcely ever be of value in diagnosis. 

Configuration of Sputa. As a general rule, the following forms 
of sputa, which may be termed pure sputa, present a homogeneous 
appearance : 

Mucoid sputa, 

Purulent sputa, [ Homogeneous sputa> 

Serous sputa, 

Sanguinous sputa, J 

with oue exception, perhaps — the typically rusty sputa of croupous 
pneumonia; while mixtures of any two or three of these may be 
classed as heterogeneous sputa : 

Muco-purulent sputa, "] 

Muco-serous sputa, j TT 

c . V Heterogeneous sputa. 

Sero-sanguinous sputa, & r 

Sanguino-muco-purulent sputa, J 

The so-called sputum crudum of the first stage of acute bronchitis 
may be regarded as an example of a purely mucoid sputum. A 
purely purulent sputum is usually indicative of one of the following 
conditions, viz., the perforation of an empyema or any other accu- 
mulation of pus into the lungs or bronchi, pulmonary abscess, or 
bronchial blennorrhea. A purely serous sputum is found in cases 
of pulmonary oedema, and a purely hemorrhagic sputum in cases of 
severe pulmonarv hemorrhage. 

Of the heterogeneous sputa, the most important are the so-called 
nummular sputa of phthisis in the second and third stages. These 
are characterized by the fact that when thrown or expectorated into 
water they sink to the bottom and there form more or less roundish 
coiu-like disks, from which property they have received their name. 
Such sputa are muco-purulent in character, and contain imbedded 
in a more or less homogeneous mass of mucus a focus of almost 
pure pus. Quite different from these are the so-called sputa globosa 
of the ancients, which consist of fairly dense, roundish, grayish-white 
masses, secreted in old cavities which have become lined with a 
granulation-membrane. 



250 CLINICAL DIAGNOSIS. 

Very important is the presence of small, eheesy pa?'ticles, which are 
occasionally found at the bottom of the spit-cup. They vary in size 
from that of a millet-seed to that of a pea, and are observed especi- 
ally in the second and third stages of phthisis. Usually they con- 
tain tubercle bacilli in large numbers, and frequently also elastic 
tissue. 

Not to be confounded with these, however, are certain small, 
caseous masses which are at times expectorated by perfectly normal 
individuals, and also by patients suffering from acute tonsillitis, 
ozama, etc., and which probably come from the tonsils or mucous 
cysts. These were formerly regarded as tubercles, and in hypochon- 
driac individuals their expectoration may cause unnecessary anxiety. 
They are quite readily distinguished from the true caseous masses 
expectorated by phthisical individuals by the following characteris- 
tics : As a rule, they are expectorated unaccompanied by any admix- 
ture of pus or even of mucus ; rubbed between the fingers they 
emit an extremely offensive odor, which is referable to the presence 
of fatty acids; an examination for tubercle bacilli, moreover, will 
prove entirely negative. Quite characteristic, furthermore, is the 
peculiar, finely flocculent, granular appearance of the sputa seen 
after the perforation of an empyema into the lungs through a small 
aperture, which is not followed by pneumothorax. 

Occasionally, as in putrid bronchitis and gangrene of the lungs, 
and also in chronic bronchitis, ultimately leading to the formation 
of bronchiectatic cavities, an exquisite sedimentation is observed. 
Such sputa, when collected in a conical glass, usually present three 
distinct zones, the one at the bottom containing the cellular elements 
of the sputum, the second the pus-serum, and the third or superfi- 
cial layer consisting of mucus and containing many air-bubbles. 

Macroscopic Constituents of Sputum. 

Elastic Tissue. Of macroscopic constituents which may be 
observed in sputa there may be mentioned, first of all, the occur- 
rence of threads of elastic tissue and pulmonary parenchyma, which 
are seen in cases of phthisis, pulmonary abscess, and gangrene. As 
their ultimate recognition, however, largely depends upon a micro- 
scopic examination, this subject will be considered later on. 

Fibrinous Casts. Fibrinous casts are observed especially in 
cases of croupous pneumonia (Fig. 64) immediately before or after 
resolution has taken place. They are also seen in cases of so-called 



THE SPUTUM. 



251 



fibrinous bronchitis (Fig. 6*5), and in cases of diphtheria, as in the 

Latter disease the fibrinous exudation may not only attack the 
walls of the larynx and trachea, but may even extend into the 
finest ramifications of the bronchi. These casts may vary in size 
from 12 cm. in length by several mm. in thickness to small 
fragments which measure only from 0.5 to 3 cm. in length. The 
fibrinous casts observed in cases of pneumonia, usually from 



Fig. 64. 




Fibrinous coagulum from a case of croupous pneumonia. (Bizzozero.) 



the third to the seventh day, are of the latter size or even 
-mailer, being derived from the ultimate twigs of the finest 
bronchioles. Those found in the rather rare disease, fibrinous 
bronchitis, stand between these two in size, being casts of the 
smaller and medium-sized bronchi. Attention is usually attracted 
to the presence of such casts by their white color; often, however, 
they are yellowish-brown or reddish-yellow, owing to the presence 
of blood-coloring matter which has become deposited upon the 
casts, while at other times they are enveloped in mucus, when their 
recognition may become quite difficult. Such casts, when exam- 
ined more carefully, will be seen to branch dichotomously, and to 



252 



CLINICAL DIAGNOSIS. 



contain a cavity in their larger portion, while the finer branches 
appear to be soild. Microscopically they may be shown to consist 
of a large number of longitudinal and often net-like arranged fibres, 
containing blood-corpuscles and epithelial cells in their meshes. 
When treated with TTeigert's fibrin-stain they are beautifully 
resolved. Charcot-Leyden crystals have been observed by some 
in these formations. 



,.. 



Fig. 65. 




Fibrinous coagulum from a case of plastic bronchitis, (v. Jaksch.) 

Whenever it is desired to examine sputa for casts it is best 
to pick out particles that look promising upon a dark or light 
surface, and then to shake these out in water in order to unravel 
them. For such purposes Kronig's sputum-plate can be strongly 
recommended. 

Curschmann's Spirals. Quite distinct from the formations 
just described are the so-called spirals of Curschmann, observed 
especially in cases of true bronchial asthma, but also occurring in 
chronic bronchitis, and even in croupous pneumonia. Upon care- 
ful examination they will be seen to occur in the form of thick, 
vello wish- white masses, which exhibit a spirally twisted appearance, 
and which are characterized, moreover, by their more solid consis- 
tence and light color. [Microscopically Curschmann's spirals are 
seen to consist of a spirally twisted network of extremely delicate 



THE SPUTUM. 



253 



fibrils, containing epithelial cells and especially leucocytes, which 
have lately been shown to belong almost exclusively to the type of 
eosinophiles. Usually, but not invariably, Charcot-Leyden crystals 
are also seen. The spirally twisted mass is found to be wound 
around a central, very light and clear thread, which usually has 
a zig-zag course (Fig. 66). 

Fig. 66. 






A Curschmann's spiral from a case of true bronchial asthma. 

Other formations, probably mere varieties of those just described, 
have also been observed, in which the central thread is absent or 



Fig. 67. 



Fig. 




€> ^°o / 



© 




Charcot-Leyden crystals. (Scheube.) 



Wall] or a hydatid cyst, showing 
the laminated structure, not mag- 
nified. (Davaine.) 



id which the spiral arrangement is deficient. The spiral form, 
however, with the central thread, must be considered as the most 
characteristic. Their length and breadth may vary a great deal, 
but rarely exceed 1 to 1.5 cm. Their occurrence seems always to 
indicate a desquamative catarrh of the bronchi and alveoli, but 
practically nothing is known concerning their formation. If, in a 
given case, the diagnosis rests between true bronchial and what may 
be termed reflex asthma, the presence of these formations points to 



254 CLINICAL DIAGNOSIS. 

the existence of the former disease. Chemically the spirally wound 
mass seems to consist of a mucinous substance, while the central 
thread is possibly of fibrinous origin. 

Charcot-Leyden crystals (Fig. 67), which are usually absent at 
the beginning of an attack of asthma, at which time only the 
spirals are observed, may be seen to develop from the spirals 
when these are kept for several days. They will be considered 
later on, in studying the chemistry of the sputum. 

Echinococcus Membranes. Echinococcus membranes come 
from a perforating cyst of the liver, kidney, or lung. They con- 
stitute rather thick, and at the same time tough, pieces of mem- 
brane (Fig. 68); occasionally entire sacs are seen, of the color of 
white porcelain, in sections of which it is possible to make out a 
fibrillated structure. They are rare in this country. 

Concretions. Still rarer is the expectoration of concretions 
which have formed in dilated portions of the bronchi or in tuber- 
cular cavities, or of calcified bronchial glands that have found 
their way into the lungs. Curious examples of the occurrence of 
such concretions have been reported. Andral thus cites a case of 
phthisis in which within eight months as many as 200 stones were 
expectorated, and Portal mentions a case in which 500 were thus 
expelled. 

Foreign Bodies. Foreign bodies which have accidentally entered 
the air-passages and have remained there for a long time are also 
occasionally found in the sputum. Heyfelder mentions a case 
in which a man coughed up a wooden cigar-holder with pus and 
blood after eleven and a half years. 

Microscopic Examination. 

Under this heading it is necessary to consider leucocytes, red 
blood-corpuscles, epithelial cells, elastic fibres, corpora amylacea, 
parasites, and crystals. 

Leucocytes. Leucocytes, usually polynuclear in character, are 
found in every sputum in considerable numbers, imbedded in a 
homogeneous, more or less tenacious material. At times they ap- 
pear very granular, containing fat-droplets in their interior, or 
granules of pigment, such as carbon, or hsematoidin. Most inter- 
esting is the occurrence of large numbers of eosinophilic and even 
of basophilic leucocytes in asthmatic sputa. The number of leuco- 



THE SPUTUM. 255 

cytes varies a great deal, being naturally greatest in cases of perfo- 
ratiiig abscess, empyema, putrid bronchitis, etc. 

Red Blood-corpuscles. The presence of red blood-corpuscles 
in small numbers does not by any means indicate serious pulmo- 
nary or cardiac disease, as they are found, according to v. Jaksch, 
in almost every sputum, and especially in that of individuals who 
smoke much or live in a smoky atmosphere, being, without doubt, 
derived from the catarrhally inflamed bronchial or tracheal mucosa. 
Whenever they occur in large numbers, however, their presence be- 
comes importaut. They may thus be observed in acute bronchitis, 
pneumonia, oedema of the lungs, bronchiectasis, abscess, gangrene — 
in fact, in all pulmonary diseases. Their occurrence is most impor- 
tant iu phthisis, being, in fact, one of the most constant symptoms 
of the disease. 

The form of the red corpuscles will depend upon the length of 
time that they have remained in the lungs, and all gradations from 
the typical red corpuscle to its shadow, or even fragments, may thus 
be observed. In pneumonia the microscopic examination may at 
times be disappointing, the appearance of the sputum suggesting 
that red corpuscles in large numbers are present, while, as a matter 
of fact, they are almost all destroyed, the color being due to altered 
pigment. It may even be necessary at times to depend upon 
chemical methods to clear up any doubt as to the source of the color 
of the sputum. It should always be remembered that the presence 
of blood-pigment is not always indicated by a red color, but that it 
may also assume a golden-yellow or even a greenish tinge, having 
undergone certain chemical changes. The golden-yellow and the 
grass-green sputa observed in cases of pneumonia during conva- 
lescence are of this class. 

Epithelial Cells. Epithelial cells may also be observed in the 
sputum. While a great deal of information would be expected 
from their presence from a diagnostic point of view, as accurately 
indicating the parts of the respiratory tract attacked by disease, the 
data obtained are of little value. 

Cylindrical epithelial cells, providing they do not come from the 
nose, indicate in a general way an inflammatory condition of the 
lower larynx, trachea, or bronchi. They are not of much impor- 
tance, however, their form being usually so much altered that it 
is often difficult to recognize them, having become polyhedral, 
cuboidal, or even round, so as to be hardly distinguishable from 



-'-_'_ 



: i :: v ; . 



-:■: >_~5 



a leucocyte. Actively moving alia can be found only in perfectly 
fresh sputa, imm ------ - iftei sing -:-:: : :_£cL If ciliated epi- 
thelial cells can be definitely recognized in a sputum, it may be 
inferred that we are dealing with a pathologic condition of an acute 
nature, providing, of course, they did not come from the nose. 



_- :.- : - 






:-" 



n : 
- : : 






<^, I 



^ 











: — r:: : ' : ■'-'' i - 1 _-- 


. • -~- - - : — 


::::'-:;:- 


-: i:-. — h-,r\ i_z : rjTLil: i ~ "1 


— i:z- - - —'zlz-i: :.:■:>',-: ::z :.i:.T- ; ; :rl rilcoi- 


: : :~~ ; ■ :.r 


■ ^:zi^:-5 rtitl-r^^l 


" ."ilS.-H 


Muc 


ii in:::-: r:,:!! it ~:~ fir: 


nerly attached to the so-called alveolar 


-. .. : " : : " 


11 _T 1 i.' . . :' z 


aid in diagnosis. Buhl thus imagined 


- _;_ - 


v- — ' - -" -. -" -- — '- ^ 


ergoing fatty or myeline degeneration, 


:: ":•- : 


;s:-li::r> .::•:_ : ^ n : m_ .: 


lie of pulmonary disease, and especially 


:•: :i;.: 


form of pneumonia i 


which has been termed essential idio- 


_.-_-.:. 


:..:»■ 11:11: :::""t :n:i:ii: 


mia. Bizzozero, however, as well as 


: : _ - i> . 


is-. « -_ "i: :__:: :.r-rs*r 


cells do not only occur in almost every 


__ . _ _ 


pulmonary disease. 


but also in the so-called ^normal" 


r :: ' t : : 


11:1 :■_ -..:: ::: :: ::i_: 


ES IS -".••-- UDC fflMBTimy f\ verv 


-•-■_- 


1 




- 




-> "^ f^* J'g 9 


".". ".""". 11. 


; 1 1: s : : - : : : n: _ . . ~ : 


oil ul 1 bev may contain one, two, or 



The latter are usually hie 

:f :::-!-- . - ir-r i'..:-': 

:: :.ir f .'_":— :::,=: :::-^ ::i:- 

LlVrllZr ^11 ■".'.".- — . ..It 



-11::- :..- .. : 1: vi :tI ~ ::.: zmiIt:'.:. 
eath numerous granules. Some 
but most of them belong to one 
ited granules, fatty granules, and 

■'.: '.'.»..\"5 ~'7i: r.i>: i:s: :TT.-ri 17 



Virchow in 1854, and termed myeline granules on account of their 
resemblance to mashed nerve-matter. They are distinguished from 
the other forms by their dear, pale, colorless appearance and the 



THE SPUTUM. 257 

fact that at times fine concentric striations can be detected. These 
forms may he round, but more often they are irregular in form. At 
times fatty, myeline, and pigment granules may be seen in one and 
the same cell. Possibly they are derived from the pulmonary alve- 
oli, but this is still an open question. 

Liver-cells may at times be observed in the sputa in cases of liver- 
abscess, and are easily recognized by their characteristic form. 

Elastic Tissue. Much more important from a clinical stand- 
point are the elastic fibres and shreds of elastic tissue which may 
be found in sputa. They vary very much in length and breadth 
and are provided with a double, undulating contour; they are usu- 
ally curled up at their ends. Very often they exhibit an alveolar 
arrangement (Fig. 70), which at once determines their origin. 

Fig. 70. 



Elastic fibres in the sputum (eye-piece III., objective 8 A, Reichert). (v. Jakshc). 

Whenever present, elastic tissue is an absolute indication that a 
destructive process is going on in the lungs. It is found in cases 
of abscess of the lung, bronchiectasis, occasionally in pneumonia, 
and, most important of all, in phthisis. In gangrene of the lung, 
elastic tissue is usually not found, probably owing, as suggested by 
Trau be, to its destruction by a ferment. 

In every case it is necessary to determine whether the elastic 
tissue may not be owing to the presence of animal food in the 
sputum, and it may, hence, be stated as a safe rule that it can only 
be regarded as absolutely characteristic when showing the alveolar 
arrangement. 

In order to demonstrate the presence of elastic tissue in the 
sputum it is necessary to examine large quantities with a moder- 

17 



258 CLINICAL DIAGNOSIS. 

ately low" power, best after the addition of a strong solution of 
sodium hydrate. The sputum may also be boiled with a 10 per 
cent, solution of the reagent, an equal volume being added; after 
dilution with four times its own volume of water it is allowed to 
settle for twenty-four hours. The centrifugal machine will here 
be found of great assistance. 

The following method, in use at the Johns Hopkins Hospital, is 
most convenient : "A small amount of the thick, purulent portion 
of the sputum is pressed out into a thin layer between two pieces of 
plain window-glass, 15 by 15 cm. and 10 by 10 cm. The particles 
of elastic tissue appear on a black background as grayish-yellow 
spots, and can be examined in situ under a low power. Or the 
upper piece of glass is slid off till the piece of tissue is uncovered, 
when it is picked out and examined on a microscopic slide, first 
with a low and then with a higher power. At first there will be 
some difficulty in distinguishing with the naked eye between elastic 
fibres and particles of bread, or milk-globules, or collections of epi- 
thelium and debris, but with practice such mistakes are rarely made, 
and the microscope always reveals the difference." (Musser.) 

Animal Parasites. 

Portions of echinococcus cysts, viz., pieces of membrane (Fig. 69) 
and hooklets (Fig. 71), are occasionally seen, when the parasite has 
lodged in the lungs or in the neighboring organs. The disease, 
however, is exceedingly rare in this country. 

Fig. 71. 






Hooks from taenia echinococcus. x 350. 



The adult parasite (Fig. 72), taenia echinococcus (v. Siebold), is 
found in the intestinal canal of dogs. It measures from 3 to 5 mm. 
in length. If the eggs of the parasite are introduced into the diges- 



THE SPUTUM. 



259 



rive tract of man, the embryos may make their way into the lungs, 
liver, or other organs, and there give rise to the formation of cysts, 
which are often of enormous size. 




Human echinococcus. (From Finlayson, after Davaine.) A, a group of echinococci, still 
adhering to the germinal membrane by their pedicles. X 40. B, an echinococcus with head 
invaginated in the body. X 107. C, the same compressed, showing suckers and hooks of the 
retracted head. D, echinococcus with head protruded. E, crown of hooks, showing the two 
circles. X 350. 

Trichomonades have at times been observed in cases of gangrene 
of the lung and in the pus removed post-mortem from lung-cavities. 
They are identical with the trichomonas vaginalis of Donne. Most 
important is the presence of the amoeba coli, as the diagnosis of hepa- 
tic abscess with perforation into the lung may be made in every in- 
stance in which this organism is encountered in the sputa (see Feces). 

A certain form of pulmonary disease, closely simulating phthisis, 
is very common in Japan, and has been shown to be referable to the 
presence of a distinct parasite in the lungs, the distoma pulmonale, 
Biilz: sytK, distoma Westermanni (Kerbert), distomi Ringeri (Cob- 
bold). The worm and its ova are found in the sputum. " The 
parasite is 8 to 10 mm. long, 5 to 6 mm. wide, of a club shape, 
rounded off very markedly in front, less rounded posteriorly. The 
color during life is almost like that of earth-worms. The two suck- 
ing disks are almost equal in size. The ova are brown, with a 
thin -hell, lidded, 0.1 mm. long and 0.05 mm. wide." (Huber.) 

In this country the parasite has been found in the cat and in the 
dog; in the human being one case at least, occurring in a Japanese 
student, has already been reported. 

It is interesting to note that many Charcot-Leyden crystals are 
at the same time found in the sputum. 



260 CLINICAL DIAGNOSIS. 

Vegetable Parasites. 

Pathogexic Obganisms. The tubercle bacillus. The most im- 
portant vegetable parasite met with in the spina is the bacillus of 
tuberculosis. The history of the discovery of this organism, and 
the theories which were held before its pathognomonic importance 
was established, cannot be considered here. Suffice it to state that 
the study of bacteriology has given no other discovery of equal 
importance from a clinical point of view. How primitive and 
wholly inadequate the means formerly employed in making the 
diagnosis of this, the most formidable disease of modern times ! 
The presence or absence of elastic tissue in the sputa was practically 
all that physicians formerly had to guide them beyond the history 
of the patient and the results of a physical examination. The 
demonstration of elastic tissue, however, as has been pointed out, 
indicates merely the existence of a destructive process in the lungs. 
Under such conditions it was of necessity impossible to diagnose 
tubercular disease in its incipiency. It is true that cases are occa- 
sionally observed in which tubercle bacilli are never present in the 
sputa, and are only discovered post mortem. Such cases, how- 
ever, are rare, and do not in the least detract from the importance 
which attaches to careful and repeated examinations of the sputa 
in all doubtful cases. 

From a macroscopic examination it is impossible to decide 
whether or not a particular sputum is of tubercular origin. At 
times a certain sputum may have a suspicious appearance, but it 
is never possible to speak with certainty from simple inspection, 
as a mucoid sputum may contain tubercle bacilli in large num- 
bers, while a muco-purulent sputum may be entirely free from them. 
Reliance should, hence, only be placed upon a careful microscopic 
examination. When found their presence is, of course, pathogno- 
monic. A negative result, however, does not exclude the existence 
of tubercular disease. The possibility that they may be altogether 
absent from the sputum has been mentioned. In some instances 
they may be present at times and absent at others. In all cases in 
which the existence of phthisis is suspected it is imperative to make 
use of every device which may aid in their detection. In this con- 
nection the author wishes to insist strongly upon the method of 
" growing the bacilli," as it were, in the warm chamber for from 
twenty-four to forty-eight hours, and then re-examining the sputa 



THE SPUTUM. 261 

in doubtful eases, as Nuttal demonstrated beyond a doubt that the 
tubercle bacillus will multiply in the sputum itself at a certain tem- 
perature. The value of this observation is obvious, and the author 
has been able repeatedly to demonstrate their presence in this 
manner when it was impossible to detect them in the fresh sputum. 

The centrifugal machine in such cases is also useful and yields 
valuable results, the probabilities of finding the bacilli when present 
in small number being very much increased. 

If but few bacilli be present, the following procedure may also 
be employed : About 100 c.c. of sputum are boiled with double the 
amount of water to which from six to eight drops of a 10 per cent, 
solution of sodium hydrate have been added, until a homogeneous 
solution has been obtained, water being added from time to time to 
allow for evaporation. This is then set aside for twenty-four to 
forty-eight hours and examined for tubercle bacilli and elastic tissue. 

In the examination of tubercular sputa the fine, caseous particles 
described on page 250 should be carefully sought for, as they con- 
tain the largest number of bacilli. In their absence reliance should 
be placed upon the examination of a large number of preparations. 

If, notwithstanding the fact that all due precautions have been 
taken, no bacilli can be demonstrated in the sputum, and the 
clinical history and the physical signs are indefinite or negative, 
the probabilities are that we are dealing with a benign process. 
From an examination of the sputa alone in such cases it is utterly 
impossible to reach a definite conclusion. When the amount of 
sputum, moreover, is small and contains but little pus, the absence 
of tubercle bacilli in doubtful cases is less suggestive of the absence 
of tubercular disease than in cases in which the sputum is more 
abundant and muco-purulent. 

It has been pointed out that the discovery of the etiologic relation 
existing between the bacillus of tuberculosis and tubercular disease — 
notably phthisis — must be regarded as one of the most important for 
the clinician, if not the most important in itself, made by bacteri- 
ologists. This is certainly true, but the discovery of certain char- 
acteristics of the tubercle bacillus which are of direct practical 
utility in its recognition and differentiation from other organisms 
is equally important. Reference is had to the behavior of the 
micro-organism toward certain staining reagents and the difference 
which exists between.it and other bacteria, and which renders its 
recoguition an easy matter. The bacillus of leprosy might possibly 



262 CLINICAL DIAGNOSIS. 

be confounded with the tubercle bacillus, but it is so rarely met 
with that it need not be considered. 

The tubercle bacillus is essentially characterized by the difficulty 
with which it takes up basic coloring-matters and the great tenacity 
with which it retains these when once stained upon treatment with 
mineral acids. 

Methods of staining the tubercle bacillus. Various methods have 
been suggested for the purpose of staining the bacillus, all of which, 
however, are modifications of that suggested by Weigert and Ehrlich. 

1. The Weigert- Ehrlich method : A drop of sputum, or, better, one 
of the cheesy particles described, is carefully spread between two 
cover-glasses; these are then drawn apart, dried in the air, and 
passed through the flame of a Bunsen burner or of an alcohol lamp 
three times, in order to fix the preparations. At the Charit6 of 
Berlin larger quantities of sputum are spread upon slides, dried, 
fixed, stained, and examined directly in oil. In order to stain the 
specimens they are floated for twenty-four hours, face downward, 
upon a solution of aniline-water and fuchsin prepared in the fol- 
lowing manner: 

A small test-tube full of water is shaken for some time with 
about twenty drops of pure aniline oil (1 : 20), and then filtered 
through a moistened filter after standing for a few minutes. To 
this solution a few drops of concentrated alcoholic solution of fuchsin 
or of methyl-violet are added until the mixture becomes slightly 
cloudy — i. e., until a slightly metallic lustre is noted on the surface. 
After twenty-four hours the preparation is washed with distilled 
water in order to remove an excess of the staining-fluid. The prepa- 
ration is then immersed for several seconds in a dilute solution of 
nitric or hydrochloric acid (1 : 6, 1 : 3, or 1 : 2), and washed again 
with water or with absolute alcohol. At this time the preparation 
should have a faintly red or violet color. It is then dried between 
layers of filter-paper or in the air, and mounted in a drop of water. 

If it be desired to make a double stain, which may at times aid 
in the recognition of the organism, Bismarck-brown, vesuvin, or 
methylene-blue in watery solutions may be used for this purpose. 
Into this solution the specimen is placed after treatment with nitric 
acid and washing in water. 

2. Gabett's method : The dried preparation is placed for two min- 
utes in a solution composed of 1 part of fuchsin (S), 100 parts of a 
5 per cent, solution of carbolic acid, and 10 parts of absolute alco- 



PLATE IX. 



FIG. 1. 



.v <&'* 






Tuberculous Sputum Stained, by Gabbett's Method. The Tubercle Bacilli 
are seen as Red Rods, all else is Stained Blue. (Abbott.) 



FIG. 2. 




I. SCHMIDT, FEC. 



The Diploeoecus Pneumoniae, Stained with Methylene Blue and Fuehsin 

as a Counterstain. Taken from the Sputum of a Case of 

Acute Croupous Pneumonia. 

FIG. 3 



<«? 









vV-w + v ' 



<*&■ 



S* 



&* 



Heart-Disease Cells, showing Alveolar Epithelial Cells, Loaded Down 
with Granules of Haematin. 



THE SPUTUM. 263 

hoi, and then immediately transferred for one minute to a solution 
of 2 parts of methylene-blue in 100 parts of a 25 per cent, solution 
of sulphuric acid. It is then washed with water and mounted. 
This method of staining the writer regards as the most convenient. 

3. Ziehl-Neelsen's method : A mixture of 90 parts of a 5 per cent, 
solution of carbolic acid and 10 parts of a concentrated alcoholic 
solution of fuchsin is used. The procedure to be followed is the 
same as that described under the Weigert-Ehrlich method. 

When method 1 or 3 is used, however, it is unnecessary to stain 
the preparation for twenty -four hours, it being sufficient to place a 
few drops of the staining-fluid upon the cover-glass and to boil this 
for a few seconds over the free flame, when the specimen is further 
treated as described. In this manner excellent results may be 
obtained in a few minutes. 

Stained according to one of these methods, the bacilli appear as 
rods measuring about 3 fi to 4 fi in length by 0.3 fi to 0.5 p. in 
breadth (Plate IX., Fig. 1). Usually they are not swollen at 
their extremities, but simply rounded off. They form homogeneous 
rods or may present within their stained bodies small round or ovoid 
granules placed end to end, which do not stain. They may also 
have a straight or a curved form, or the bacillus may appear to be 
doubled upon itself in the form of the letter S. The small, hyaline 
bodies in the bacilli have been regarded as spores. 

The number of bacilli which may be found in a sputum varies 
greatly, and while in general it may be said that it is in direct 
ratio to the intensity of the disease, and may thus be considered as 
of some prognostic value, too much reliance should not be placed 
upon this statement, as in acute miliary tuberculosis, and in cases 
that have gone on to the formation of cavities the walls of which 
have become dry and cicatrized, the number found may be very 
small or they may be altogether absent. In an incipient case, on 
the other hand, in a little mucoid sputum the number may be very 
large. 

Of the variations in number and form of the tubercle bacilli dur- 
ing the treatment with Koch's tuberculin it is unnecessary to speak 
here, as the prognostic significance attaching to such variations is as 
yet but imperfectly understood. 

The diplococcus pneumoniae. In doubtful cases the sputum may 
be examined for the diplococcus pneumoniae, and it may be accepted 
at the present time that its presence in a given case, providing that 



264 



CLINICAL DIAGNOSIS. 



the clinical history and the physical signs point to a pneumonia, 
renders the diagnosis of acute croupous pneumonia very probable. 

Method: Cover-glass specimens, prepared as indicated above, are 
placed for one or two minutes iu a 1 per cent, solution of acetic acid; 
they are then removed, the excess of acetic acid drawn off by means 
of a pipette, when they are allowed to dry in the air and subse- 
quently placed for several seconds in saturated aniline- water and 
gentian-violet solution, washed in water and examined. Rod- 
shaped diplococci (Plate IX., Fig. 2) surrounded by a capsule, 
which latter is considered as the characteristic feature of this 
microbe, will be seen in cases of acute croupous pneumonia. 

The bacillus of influenza has already been considered in Chapter 
I. (p. 86). _ 

In whooping-cough protozoa have been observed by Deichler; his 
observations, however, have not as yet been confirmed, and other 
observers attribute the disease to the presence of a bacillus described 
by Affanasiew. 

Fig. 73. 





Actinomyces. (Musser.) 



Actinomycosis of the lungs may possibly be diagnosed from the 
presence of the characteristic granules and thread-like formations 
in the sputum. In America the disease is very rare. 

The organism in question (Fig. 73) probably belongs to the species 
cladothrix, occupying a unique position among the pathogenic bac- 
teria. Infection in man and animals (cattle and pigs) possibly occurs 
through ears of barley or rye, a supposition with which the observa- 
tion that the disease frequently begins in the autumnal months 
accords. 



THE SPUTUM. 265 

In the pus derived from ulcerating actinomycotic tumors, in the 
sputum in cases of pulmonary actinomycosis, as also in the feces 
when the disease has attacked the intestines, small yellow granules 
will be observed, measuring from 0.5 to 2 mm. in diameter. If 
such a granule be examined microscopically, slight pressure being 
applied to the cover-glass, it will be seen to consist of numerous 
threads, which radiate out from a centre in a fan-like manner, and 
present club-shaped extremities. 

The organism may be demonstrated in the following manner: 
Dried cover-glass preparations are stained for five to ten minutes 
with a saturated aniline- water and gentian- violet mixture (see p. 
262), when they are rinsed in normal salt-solution, dried between 
filter-paper, and transferred for two or three minutes to a solution 
of iodo-potassic iodide (1 or 2 : 100). They are then again dried be- 
tween layers of filter-paper, decolorized in xylol-aniline oil ( 1 : 2), 
washed in xylol, and mounted in balsam. The mycelium assumes 
a dark-blue color. 

Xox-pathogenic OrganiSxMS. Of the non-pathogenic micro- 
organisms which may be observed in sputa but little is known. 

O'idium albicans may be observed in children, and is usually 
derived from the mouth. 

Of other fungi w T hieh are occasionally observed in the sputum, 
there may be mentioned the aspergillus fumigatus and mucor 
corvmbifer. Saccharomyces has been seen in the pus derived from 
pulmonary abscesses. Sarcina pulmonalis has been found at times, 
and especially in the so-called mycotic bronchial props occurring in 
putrid bronchitis. They are usually smaller than the sarcinse ven- 
triculi, but larger than the sarcinae observed in the urine ; they 
present the characteristic form of the latter. Various other bacilli 
and micrococci, in addition to those mentioned, are also found in 
sputa in large numbers, but have not as yet been closely studied, 
excepting the pus-organisms, which may be almost always demon- 
strated. 

Crystals. Of crystals which may occur in sputa it will be neces- 
sary briefly to consider the crystals of Charcot-Leyden, haematoidin, 
cholesterin, margarin, ty rosin, oxalate of calcium, and triple phos- 
phates. 

Charcot-Leyden crystals (Fig. 67) were discovered in the sputa 
of patients suffering from asthma, and were supposed to stand in a 
causative relation to the disease. While the crystals are usually 



266 CLINICAL DIAGNOSIS. 

present in this disease, they are also exceptionally met with in acute 
and chronic bronchitis, phthisis pulmonalis, etc. 

Chemically, they appear to be phosphate of spermin, which has 
the composition C 2 H 5 1SF, and has been shown to be identical with 
ethylenimine. The phosphate crystallizes in the form of colorless, 
elongated octahedra, which vary very much in size, specimens being 
at times met with measuring from 40 fi to 60 p. in length. It 
is soluble with difficulty in cold water; insoluble in alcohol, ether, 
chloroform, and dilute saline solution; slowly soluble in acids and 
alkalies and even in ammonia. Its chemical composition and the 
fact that the same crystals are found in decomposing viscera, at 
times forming a complete covering of old anatomical preparations, 
render the supposition very probable that the substance in question 
is closely related to the ptomaines; the occurrence of the crystals 
may, indeed, be regarded as indicating a retrogressive metamor- 
phosis of the cellular elements of a part. They are found not only 
in the sputa in the diseases mentioned, but also in leukemic blood, 
in the mucus which has accumulated in a dilated biliary duct, and 
in normal and leuksemic bone-marrow. As has been stated, the 
crystals are also quite constantly met with in the feces in anchylos- 
tomiasis, anguilluliasis, and other helminthiases (see p. 208). Biz- 
zozero found them in his own sputum at times when suffering from 
a simple acute bronchitis. 

Hcematoidin-crystals may be observed in the sputa following 
extravasation of blood into the lung. They frequently occur in 
the form of ruby-red columns or needles (Plate I., Fig. 2); amor- 
phous granules, however, are also at times seen enclosed in the 
bodies of leucocytes, in which case they are probably always indica- 
tive of a previous hemorrhage, while the needles are generally 
observed when an abscess or empyema has perforated into the lungs. 
Chemically, hsematoidin is derived from blood-pigment, and ap- 
pears to be closely related to bilirubin. 

Cholesterin-crystals are at times seen in the sputa in cases of 
phthisis, pulmonary abscess, and in general whenever old accumu- 
lations of pus have entered the lung from a neighboring organ. 
They are readily recognized by their characteristic form and 
chemical properties (see Feces, p. 195). 

Fatty-acid crystals are frequently observed in cases of putrid bron- 
chitis and gangrene of the lung, and also in cases of bronchiectasis 
and phthisis. They occur in the form of single needles or groups 



THE SPUTUM. 267 

of needles which are long and pointed. They are easily soluble in 
ether and hot alcohol; insoluble in water and acids. Chemically, 
they are probably composed of the higher fatty acids, such as pal- 
mitic and stearic acids. 

Ty rosin-crystals have been observed in cases of putrid bronchitis, 
perforating empyema, etc. Leucin is likewise probably always 
present, occurring in the form of highly refractive globules. For 
the recognition of these bodies, particularly of tyrosin, a chemical 
examination should always be made, as crystals of the soaps of fatty 
acids have frequently been mistaken for those of tyrosin (see Urine). 

Oxalate of calcium crystals are rarely seen. Ftirbringer observed 
them in large numbers in a case of diabetes, and Unger found them 
in a case of asthma. They are readily recognized by their envelope- 
form, but they occur also in amorphous masses. They are soluble 
in mineral acids; insoluble in water, alkalies, organic acids, alcohol, 
and ether. 

Triple phosphate crystals are also, though very rarely, seen, as in 
cases of perforating abscesses, etc. They are recognized by their 
coffin-lid shape and the readiness with which they dissolve in acetic 
acid. 

Chemistry of the Sputum. 

In addition to the substances described, sputum contains certain 
albumins, volatile fatty acids, glycogen, ferments, and various in- 
organic salts. 

Among the albumins which have been observed in sputa may be 
mentioned serum-albumin, and especially mucin, which is often 
present in large amounts. In pneumonic and purulent sputa pep- 
tone also has been found. 

In order to demonstrate the presence of serum-albumin the sputa 
are treated with dilute acetic acid, when the filtrate may be tested 
with potassium ferrocyanide, as described in the chapter on Urine. 
Serum-albumin is, of course, found in notable quantities in cases of 
oedema of the lungs. 

The volatile fatty acids contained in sputa may be obtained by 
diluting these with water, acidifying with phosphoric acid, and 
distilling, when the distillate is further examined as described in 
the chapter on Feces. Acetic, butyric, propionic, and capronic 
acids have been found. 

The fats or fixed fatty acids are extracted from the residue with 



ether, and shaken with a solution of sodium carbonate in order to 
transform them into their sodium salts, when the ether is decanted 

zzz zzzz zzzzi. ift_viz^ :':t zzzi zfizizzl 

Glycogen has been repeatedly demonstrated in spnta and may be 
detected by Brooke's method. (See p. 46.) 

Xzz izzzz :_ zzzzzt :■_ zif izzzz^; f-i zzzz brzzzzizii zzvz 
ffz iz; — z :: zzzz: : zfrzzfz:: : — z z:__ r: -.I Ir. :: if: : 
zf_: ::: zizii fzrzzfz: :i:z izzz: ::z tz:z: zfi — izz ^ivzzrizzz. iii zzz 

t:::„::::.:i : ; ::::;::t:" :• iffZ-ii-fi in zzf izzzzz: ::::rEiiz- 
z_z z : z : . "?zi : .'•: izi:^. 

~zf z:ii: .z_ _rf zzf izir^zzi: i;zizi — iziziz zzzj zf zzzz :z.:z;:f i 

:i : „ - « * zz: zz __ z T ; _ z z .z . " : «■» "«z ~ v zz . zz : ^ ...-.--"_ " z : _ z z : : - _ 

:: tiff z z ..-- . _ z : . . : _z: .:i: ft; : :.z= viz :: . : izzz ; : zzz^zzfsizzz. 
:it -:>::::t« :■: zi :: zzz z~z i - ; z zzz. z.;z:z:«.:::zz.z :::zz. 
zzz -zzz:ff 



jLf-Zf -::: 



zzrzzzfz z_ -zzz.. zz zzz:v_z z::^ zz:". zzz vz:izi: vfr~ z-~~ 
"-_z.:z: t.tZtIZ zzzszizzzzZi zzz .z -zz.- z ; : . . _~: zzz 

zzzifzzf. iizzzz z zz._~ zzzf Li rzzz ::' :zt fxifZfzzf :: z 
ifs: zzzzzziv- zzzz-. zziz:; z:~zrz :zt zzizz:zz:;- _ivf-;i; :■: z 
^_z~.: :r Iffi fxzcz: :zz z -_zzz_ f. fiiziijzizf . z :"_: .: : :. . z ...t." 
Ezizizfiizi filf : ::.: - :z:z_- z. zzzz. zzz zzf rr:zzbiv 
ZtZZ'tZ zrzzz :.__- ~~ zzz. ~f.f :z:_vz.z' ziizifi. 'I'ziizz- . -fiif 
:_:;• zz..._ ziij >_ : .:• zz- .. zz ZtZzz;- zzffz fzzoizzfzz ' :: 
z: z v_.zz.ii_ - z Lffz:. Lzzzzz-z iz izzzii z:z:iz- zzizizzizz >zii_ 
zzz zifz ffrz. Tzf z zfSrZ zz ,i : ff— .-'. :i: ".-::. zzifi is z 
common occorrenee, and probably doe to rnptnre of a capillary 
z i :■: :i"f f f -i L.zz- :z zizf szzzz zzzz zzz z_ : . . zzzzzzz. :zz if. 
zi zss zzzz -7-- " ::i:: :f_:\z_ z: gr-ffz. :~vz_ :: z :z:.t : . . iz 
~ - z "" z_ " - : - "';■'"" ■ "- - Z-Z-f zzz zzzf : ._ . v . - -zz-z:^ ■ — - — - - 

Cizrizz: 5r:_:izir_£ 7z. zzz:zzi: zz'. _-:-zz: : zizz vzz:z 
iz zz:- zz'zzzz ~zrj vrfzzi" i: i_ z. z: z :zizz: iz zz-- :: -z 
zzz. :: z z zz ft iz "... z ~ z _t zz:zz"zfzif z.:j . . zzz - 
xated at a time. The color is usually a yellowish-green, owing to 

:iif zzfffzzf :: zzzzz: z z- - . - -z.t- :: izz-v- 

:zz z. i iz: z - z-zz' -rz.iz:. zzz/'-z- : zzi:z:-: zrf zifzzf z:f 
: :z : ff z»f ziziiv iz zziff iz ~z: . : f f v .. ' rfzzzizf . : z f:izz 



THE SPUTUM. 269 

length of time in the bronchi. In addition some red corpuscles and 
epithelial cells are found; the latter, however, are not so abundant 
as in the first stage of an acute bronchitis. A few alveolar epithe- 
lial cells in a state of fatty and myeline degeneration will also 
usually be discovered, as in the case of acute bronchitis. 

Putrid Bronchitis and Pulmonary Gangrene. The sputa of 
putrid bronchitis and pulmonary gangrene resemble each other so 
closely that it is only possible to distinguish between the two by the 
presence of debris of pulmonary parenchyma in the latter disease. 
In pulmonary gangrene an exquisite sedimentation is also quite com- 
monly observed when the sputum is placed in a conical glass, the 
bottom layer being of a greenish-yellow or brownish color, contain- 
ing a large amount of pus and small greenish or brownish masses, 
varying in size from that of a millet-seed to that of a bean. Frag- 
ments of lung-tissue are also quite frequently seen. Microscopically 
more or less degenerated leucocytes, crystals of ammonio-magne- 
sium phosphate, and perhaps also of tyrosin and leucin, as well 
as haematoidin, are found. The greenish or brownish masses referred 
to contain amorphous masses of pigment, probably derived from 
haemoglobin, at times elastic tissue, fatty-acid crystals, fat droplets, 
and innumerable micro-organisms, among which the leptothrix pul- 
monalis is quite conspicuous, and may be recognized by the violet 
or bluish color which it assumes when treated with Lugol's solu- 
tion. Most important in the differential diagnosis between this 
affection and putrid bronchitis is the occurrence of elastic fibres 
arranged in an alveolar manner. The middle layer is whitish, 
transparent, and contains flakes of mucus in suspension. The 
superficial layer is frothy and of a dirty greenish-yellow color, the 
entire mass emitting an odor never to be forgotten. 

Fibrinous Bronchitis presents all the characteristics of an ordi- 
nary chronic bronchitis; the sputa, however, contain in addition 
well-defined fibrinous casts, which have been described (see p. 250). 

Bronchial Asthma. In this affection, and especially at the com- 
mencement of an attack, the expectoration is scanty, frothy, and 
grayish, or at times rose-colored, owing to an admixture of blood. 
Most characteristic are plug-like masses of a greenish-yellow or gray- 
ish color, containing spirals of Curschmann, Charcot-Leyden crystals, 
and a large number of eosinophilic and some basophilic leucocytes. 

Pulmonary Abscess. The sputum as long as it is fresh does 
not emit a fetid odor, thus differing from that observed in cases 



270 CLINICAL DIAGNOSIS. 

of gangrene of the lung. It consists almost entirely of pus; elastic 
fibres are present in abundance, as also brownish or yellow pigment- 
hsematoidin. Fragments of lung-tissue enclosed in a mass of pus 
have at times been observed, together with fatty-acid and choles- 
terin crystals. 

Abscess of the Liver with Perforation into the Lung. The 
sputa are of a reddish-yellow or reddish-brown color, viscid and 
muco-purulent, being frequently discharged in large amounts. 
Microscopically, pus-corpuscles, red blood-corpuscles, pigmented 
alveolar cells, often undergoing fatty degeneration, as well as 
elastic tissue and granular detritus, are found. The presence of 
actively moving aincebse is, of course, most important from a diag- 
nostic point of view, and is at the same time absolutely pathogno- 
monic. Liver-cells, pieces of echinococcus-membranes, and hook- 
lets may be observed in other cases. 

Pneumonia. During the first and third stages a simple catar- 
rhal sputum is observed which does not offer any special characteris- 
tics. During the second stage, however — i. e., that of hepatization — 
the sputum is usually quite characteristic. Its color is then reddish- 
brown — the classical rust-colored expectoration. The sputum at the 
same time is generally so tenacious that the spit-cup can actually be 
inverted without losing a drop of its contents. Microscopically the 
following elements may be found : red corpuscles (to the presence 
of these the reddish color is principally due); at times, however, 
only a small number is observed, when the color is referable to 
haemoglobin which has been dissolved out from the corpuscles, and 
in such cases but few, if any, corpuscles are found. Leucocytes are 
always present in considerable numbers. Fibrinous casts of the 
finer bronchioles may also be seen, and may, in fact, be visible to 
the naked eye. Alveolar epithelial cells, often loaded with granules 
of pigment, fat, and myeline, as well as others derived from the 
larger bronchi and the trachea, are also seen. Should abscess of the 
lung or gangrene complicate the case, the elements described above 
under these headings will be found in addition, the presence of 
elastic tissue being, of course, the most important. 

Xote may be taken at the same time of the occurrence of pneu- 
mococci, bearing in mind, however, that their presence is not abso- 
lutely pathognomonic. In doubtful cases, as indicated, their pres- 
ence may be regarded as pointing to croupous pneumonia, pro- 
viding that the clinical history and the physical signs are in accord. 



THE SPUTUM. 271 

Phthisis Pulmonalis. The appearance of the sputum in phthisis 
offers nothing that is characteristic';, depending wholly upon the stage 
of the disease, its extent, the existence of complications, etc. In a 
general war it may be said that the sputa in incipient cases are 
usually small in amount, of a grayish-yellow color, and tenacious, 
the amount increasing gradually as the disease progresses, the largest 
quantities at this stage being expectorated in the morning upon 
rising. When well advanced the nummular sputa are seen. The 
macroscopic examination of the sputa of tubercular patients offers 
no characteristic features, the elements found being practically the 
same as those observed in cases of simple chronic bronchitis, with 
one exception — i. e., the occasional admixture of blood, which is 
usually visible to the naked eye, but may vary greatly in amount. 
On the one hand, small specks or streaks of blood may be thus 
observed, while, on the other, the sputa may consist almost entirely 
of blood. The color of the sputum is, of course, largely influenced 
by the amount of blood present and the length of time that 
this has remained in the lungs, varying from a bright red to a 
dirty brown. In cases in which a considerable hemorrhage has 
taken place it is, of course, necessary to exclude every other source 
before attributing the hemorrhage to a pulmonary origin, and in 
cases of rupture of an aneurism, or long-continued hyperasmic con- 
ditions of the lungs so frequently observed in cases of heart-disease, 
in hemorrhage of gastric origin, and in hemorrhage from the mouth 
or pharnyx, it may at times be difficult to determine the source of 
the blood. 

The diagnosis of phthisis is thus altogether dependent upon a 
microscopic examination, and, above all, upon the demonstration of 
the presence of tubercle bacilli and elastic tissue, which have both 
been considered in detail. In addition leucocytes, alveolar epithe- 
lial cells, haBmatoidin-crystals, and granules are met with, which 
latter may be present in large numbers if a hemorrhage have 
occurred some time before. If the process has gone on to the 
formation of cavities, various constituents are also observed point- 
ing to putrefactive processes taking place in the lung. 

CEdema of the Lungs. The sputa here are abundant, thin, 
liquid, and frothy, the color of the foam varying from white to a 
dirty reddish-brown. Chemically, such sputa consist almost entirely 
of transuded serum, and are hence particularly rich in serum-albu- 
min. Microscopically, only a small number of leucocytes and a 



272 CLINICAL DIAGNOSIS. 

variable number of red blood-corpuscles are found, the number of 
the latter, however, being scarcely large enough to account for the red 
color, which v. Jaksch ascribes to the presence of methsemoglobin. 

Heart-disease. The sputa observed in chronic bronchitis the 
result of chrouic heart-disease are characterized by the presence of 
so-called "heart-disease cells " — i. e., alveolar epithelial cells con- 
taining numerous hsematoidin-granules (Plate IX., Fig. 3). If, in 
consequence of the existence of chronic heart-disease, hemorrhagic 
infarcts have occurred in the luugs, the patient may at times expec- 
torate numerous masses presenting a markedly red color, while later 
on — i. e., after several days — these masses assume a brownish-red 
appearance, the sputum then presenting the characteristics noted 
some time after a hemorrhage. 

The Pneumoconioses. Among the pneumoconioses, anthracosis, 
siderosis, chalicosis, and stycosis may be briefly considered. These 
conditions are interesting not only from a physiologic but also from 
a pathologic stand-point. 

Anthracosis. To some extent particles of carbon may be found 
in the sputum of almost every individual, and especially in tobacco- 
smokers. The sputum in such cases is of a pearl -gray color, and is 
expectorated in larger or smaller masses, especially in the morning 
upon rising. Larger amounts are, of course, noted in miners and 
those who are brought into close contact with coal-dust. Micro- 
scopically particles of carbon and epithelial cells, especially of the 
alveolar type, as well as leucocytes, loaded with the pigment, are 
seen. 

Siderosis. In siderosis the sputum presents a brownish-black 
color and contains cells enclosing particles of the oxide of iron. 
These may be readily recognized by treating the preparation with a 
drop of ammonium sulphide or potassium ferrocyanide solution in 
the presence of hydrochloric acid, when a black color on the one 
hand or a blue color on the other is obtained in the presence of 
iron. 

Chalicosis. In chalicosis silicates are found in the sputa. 

Stycosis. This condition was described for the first time by A. 
Robin in a man, aged seventy, who from his seventeenth year suffered 
from cough and frequent attacks of diarrhoea, and whose condition 
had been diagnosed as phthisis pulmonalis et intestinarum at various 
times, no examination having been made for tubercle bacilli. The 
patient died from acute pericarditis complicating an attack of acute 



THE SPUTUM. 273 

mono-articular rheumatism. Post mortem the lungs were found to 
be perfectly normal; the bronchial and anterior mediastinal glands, 
as well as the mesenteric glands, however, were completely solidi- 
fied and composed almost wholly of calcium sulphate. The man, 
it was then found, had been working in plaster-of-Paris all his life, 
and the symptoms observed — viz., cough, expectoration, and diar- 
rhoea — Robin is inclined to attribute to pressure of the solidified 
glands upon the bronchi and intestines. 






CHAPTEE VII. 

THE URINE. 

GENERAL CONSIDERATIONS. 

This is not the place to enter into a discussion of the various 
hypotheses winch have been advanced from time to time to explain 
the manner in which waste-material is removed from the body 
through the kidneys. It will be sufficient to state that, while the 
water and mineral constituents of the urine undoubtedly pass into 
the uriniferous tubules by a process of transudation, a selective 
glandular activity of the cells lining the convoluted tubules and 
the loop of Henle, at least, appears to be necessary for the elimina- 
tion of the most important organic constituents. 

As the physical characteristics of the urine, as well as its chem- 
ical composition, are influenced not only by the age and sex of the 
individual, but also by the character of the food ingested, the pro- 
cess of digestion, exercise, climate, temperature, race, etc., it is ap- 
parent that a quantitative analysis of any one urine, or even average 
figures, can give only an approximate idea of its composition. The 
reader is referred for information to the special paragraphs concern- 
ing the variations in the individual constituents observed in health. 
It is important, however, to note that, notwithstanding the fairly 
wide variations here observed, the composition of the blood, as 
already pointed out in a previous chapter, remains quite constant, 
showing the perfect manner in which the nervous system through 
the kidneys guards against an undue accumulation of what may be 
termed normal waste-products in the blood, and in virtue of which 
abnormal substances are also immediately eliminated. Moreover, 
as will be pointed out later on, a perfect mechanism appears to exist 
which prevents an undue accumulation of material in the blood that 
can hardly be regarded as waste. The presence of an amount of 
sugar in the blood exceeding 6 p. m., for example, appears to be 
invariably followed by glycosuria, and the introduction of excessive 
quantities of sodium chloride similarly and almost immediately leads 
to an elimination of the excess. 



THE URIXE. 275 

GENERAL CHARACTERISTICS OF THE URINE. 
General Appearance. 

Normal urine, just voided at an ordinary temperature, is either 
perfectly clear or but faintly cloudy, owing to the fact that the aeid 
and normal salts present are all soluble in water. It maybe stated, 
as a general rule, that whenever a urine freshly passed manifests a 
distinct cloudiness some abnormality must exist. 

When allowed to stand for a time a light cloud is seen to develop, 
which gradually settles to the bottom, constituting the so-called 
nubecula of the ancients. Examined under the microscope this is 
found to contain a few round, granular cells, somewhat larger than 
normal leucocytes, the so-called mucous corpuscles, and a few pave- 
ment-epithelial cells, derived from the bladder or genital organs. 
Chemically the nubecula probably consists of traces of mucus. 

When kept for twenty-four hours at an ordinary temperature some 
crystals of uric acid are frequently observed in addition to the above 
elements, usually presenting the so-called w r hetstone-form. If, how- 
ever, the temperature at which the urine is kept approaches the 
freezing-point, the entire volume of urine becomes cloudy, owing 
to a precipitation of acid urates. As these are very much less sol- 
uble in cold thau in warm water, they gradually settle to the bottom 
of the vessel, forming what is known as a sediment, while the super- 
natant fluid again becomes clear. 

If kept for a still longer time exposed to the air at the tempera- 
ture of the room, the entire volume of urine again becomes cloudy, 
owing to a diminution of its normal acidity, the result being a pre- 
cipitation of ammonio-magnesium phosphate, calcium phosphate, 
and still later, when the urine has become alkaline, of ammonium 
urate. 

Gradually a heavy sediment, containing these salts in addition to 
the constituents of the primitive nubecula, forms at the bottom of 
the vessel, the supernatant fluid, however, remaining cloudy. On 
microscopic examination it will be seen that this cloudiness is due 
to the presence of enormous numbers of bacteria. 

The changes which take place in a normal urine, when allowed 
to stand at an ordinary temperature, may thus be tabulated as 
follows: 

I. Urine clear, no sediment — reaction acid. 



276 CLINICAL DIAGNOSIS. 

II. Urine slightly cloudy, owing to the development of the 
nubecula — reaction acid. 



Nubecula ( Mucous cor Puscles, 



Pavement-epithelial cells. 
III. Urine clear, the nubecula has settled — reaction acid, 



f Mucous corpuscles, 
Sediment \ Epithelial cells, 

I Uric-acid crystals, 
[_ A few bacteria. 

IV. Urine cloudy, owing to the precipitation of phosphates — 
reaction faintly acid. 
Y. Urine cloudy, owing to the presence of bacteria — reaction 
alkaline. 

f Bacteria, 
| Mucous corpuscles, 
J Epithelial cells, 
Sediment 1 Triple phosphateS) 

I Tri-calcium phosphate, 
I Ammonium urate. 

Color. 

The color of normal urine may vary from a very light yellow to 
a brownish-red, the particular shade depending essentially upon the 
specific gravity, becoming lighter with a diminishing, and darker 
with an increasing density. Pathologically the same rule holds 
good, excepting the urines of diabetic patients, in which a very 
high specific gravity is generally associated with a very light color. 
The reaction of the urine also exerts a marked influence upon its 
color, an acid urine being more highly colored than an alkaline 
urine, which can be readily demonstrated by allowing a specimen 
of acid urine to become alkaline, and by treating an alkaline urine 
with dilute hydrochloric or acetic acid. At the same time it may 
be said that every urine darkens slightly on standing, the reaction 
remaining acid. 

The various shades observed in normal urines may be grouped 
under the following headings: 

1. Pale urines vary from a faint yellow to a straw-color. 

2. Normally colored urines are of a golden or of an amber- 
yellow. 



THE URINE. 211 

3. Highly colored uriucs present a reddish-yellow to a rod 
color. 

4. Dark urines vary between brownish-red and reddish-brown. 
As these shades may occur in both normal and pathologic urines, 

definite conclusions cannot, as a rule, be drawn from mere inspec- 
tion. A very pale urine simply indicates an excess of water, which 
maybe physiologic, but may also be associated with such diseases as 
chronic interstitial nephritis, diabetes mellitus, diabetes insipidus, 
hysteria, and the various anaemias, and may also occur during con- 
valescence from acute febrile diseases, while a highly colored urine, 
also occurring in health, may indicate the existence of some febrile 
disease. It may be stated, as a general rule, that a pale urine always 
excludes the existence of a febrile disease of any severity, and that 
the continued secretion of a very pale urine is usually associated with 
a certain degree of anaemia. 

The normal color of the urine is probably owing to the presence 
of several pigments, which are most likely closely related to each 
other and to haematin. 

In addition to these colors others may be observed at times, 
which are either pathologic or accidental — i. e., due to the presence 
of certain drugs. The former are, on the whole, of greater impor- 
tance to the physician than those mentioned above, as more definite 
conclusions can be drawn from their presence. 

Most important among such pathologic pigments are those due: 

1. To the presence of blood coloring matter. The color in such 
cases may vary from a bright carmine to a jet-black, the exact 
shade depending upon the quantity of blood coloring-matter present, 
upon any change that the blood may have undergone, either before 
or after being passed, and also upon the presence of the pigment 
in solution or contained in red corpuscles. 

2. Those due to the presence of biliary coloring-matter. The 
color of the urine varies from a greenish-yellow to a greenish-brown. 

3. A milky-colored urine is observed in cases of chyluria. 
Among the accidental abnormalities in color, on the other hand, 

are those due to the presence of substances like carbolic acid and 
its congeners, santonin, etc. 

As the recognition of the causes of such alterations, normal, 
pathologic, and accidental, largely depends upon a more detailed 
study of the individual pigments, this subject will be dealt with 
more fully further on (see Pigments). 



278 CLINICAL DIA QB . S2S 



Odor. 



The odor of the urine is usually of little significance. Normally 
it resembles that of bouillon, and in some cases that of >ysters; it 
is probably due to the presence of several volatile acids. The odor 
of urines undergoing decomposition is characteristic and has been 
termed " the urinous odor of urine,'' an ill-chosen term, this odor 
being always indicative of an abnormal condition. 

The ingestion of asparagns. onions, oil of turpenr'iir. etc, pro- 
duces a characteristic odor which is of no significance. 

Consistence. 

Urine, while normally fluid and bat slightly visci .. may in path- 
ologic conditions acquire a marked degree of viscidity, which becomes 

especially apparent upon attempting its filtration: the liquid passes 
through the paper with more and more difficulty, finally clogging 
its pores altogether. 

Quantity. 

The normal quantity of the urine is subject to great variations, 
the amount eliminated in the twenty-four hours being influenced by 
the amount of fluid ingested, the nature and quantity of the food, 
the process of digestion, the blood-pressure, the surronnding tem- 
perature, sleep, exercise, body-weight, sex, age, etc. 

It is easy to understand, then, why the figures given by different 
observers in different countries should vary considerably. Salkow- 
sky, in G-ermany, thus gives 1500 to 1700 c.c. as the normal amount; 
v. Jaksch, in Austria, 1500 to 2000 c.c. : Landois and Sterling, in 
England, 1000 to 1500 c.c; Gautier, in France, 1250 to 1300 : . :. 
In the United States the author has found an average secretion of 
from 1000 to 1200 c.c. in the adult male, and 900 to 1000 c.c. in 
the adult female. It is thus seen that the secretion of urin^ is 
greatest in Germany and Austria, where the body-weight and in- 
gestion of liquids are greater than in England, France, and the 
United States. 

Children pass less, but relatively more urine, considering their 
body-weight, than adults. 

The female passes somewhat less than the male. 

During the summer months, when a larger proportion of water is 
removed from the body through the skin and lungs than in cold 
weather, less urine is voided. The same occurs during rep:—. 



THE URINE. 279 

more urine being passed during active exercise, and hence less 
during the night than daring the day. 

The amount of urine secreted in the different hours of the day 
varies greatly, reaching its maximum a few hours after meals. It 
decreases toward night, and reaches its lowest point in the first 
hours of the night, after which it begins to rise rapidly until 2 or 
3 o'clock in the morning. 

The ingestion of large amounts of liquid, of course, increases the 
daily amount considerably, and 3000 c.c. may be passed by a man 
in good health, while it may decrease to 800 or 900 c.c. when but 
little liquid is taken. 

After the ingestion of much solid food the secretion of urine is 
temporarily diminished. 

Water containing no salts appears to possess diuretic properties, 
as do also beer, wine, coffee, tea, etc. 

The most important medical diuretics are digitalis, squill, broom, 
spirits of nitrous ether, juniper, urea, etc. 

Pathologically the amount of urine varies within very wide limits. 
It may be exceedingly difficult, however, to determine in a given 
case whether or not the secretion be within physiologic limits. As 
a general rule, whenever less than 500 c.c. or more than 3000 c.c. 
are passed some abnormal condition exists, providing all other 
causes which might lead to the secreton of such an amount can be 
eliminated. 

Clinically we speak of polyuria and oliguria. 

Polyuria. Polyuria has been observed in many different dis- 
eases, and under such varied conditions that a classification is at 
present only warrantable upon a hypothetic basis, especially as the 
causes concerned in its production are mostly unknown. 

As this condition is almost invariably associated with diabetes 
mellitus, its existence in any case should always excite suspicion 
and lead to a more detailed examination. The quantity of fluid 
eliminated in diabetes is usually dependent upon the amount in- 
gested. The excretion of a proportionately large amount of fluid, 
however, does not necessarily follow the ingestion directly, and a 
retention of a large amount may occur, it having been shown that 
the diabetic patient excretes liquids with greater difficulty than the 
healthy subject. At the same time it should be borne in mind 
that the polyuria in diabetes is not necessarily continuous, and that 
periods during which a normal or even a subnormal amount of urine 



280 CLINICAL DIAGNOSIS. 

is observed may alternate with true polyuria. From 2 to 26 or 
even 50 liters may be passed within twenty-four hours. Intercur- 
rent diseases of a febrile character may modify the amount very 
materially and cause the elimination of a normal or subnormal 
amount of urine. 

The cause of the polyuria occurring in diabetes mellitus is at 
present unknown. The ingestion of large amounts of liquids, of 
course, leads to a correspondingly large elimination, and the exist- 
ing polydipsia could, hence, be made responsible for the polyuria, 
and the latter be the result of an increased stimulation of the thirst- 
centre, possibly owing to the presence of some abnormal constituent 
of the blood. The polydipsia, however, may also be the result of a 
primary polyuria. 

The polyuria associated with the resorption of large pericardial, 
pleural, ascitic, and subcutaneous effusions is more readily under- 
stood, although the primum mobile may be unknown, depending 
in such cases entirely upon the presence of excessive quantities of 
fluid in the bloodvessels. 

A form of polyuria, which has been termed " epicritic polyuria," 
is quite frequently observed during convalescence from acute febrile 
diseases, and is of some prognostic importance. Its occurrence 
in a given case is regarded by many as a good omen, especially 
in typhoid fever; still it must not be forgotten that a polyuria 
may occur after the subsidence of the fever, and be followed by 
a considerable degree of oliguria, and in some cases may precede 
death. A polyuria of this kind probably always indicates the 
elimination of waste-products which had accumulated in the blood 
during the course of the disease, and may, at the same time, to some 
extent, be due to the presence of retained water. 

Second in constancy is the polyuria associated with granular 
atrophy of the kidneys, constituting one of the most important 
symptoms of the disease. Cases have been reported in which as 
much as 10,000 c.c. of urine were secreted in the twenty-four 
hours, although 2000 to 4000 c.c. probably represent the usual 
amount in such cases. Polydipsia exists at the same time, and 
the explanation of the polyuria again becomes a very difficult 
matter. The explanation usually given is based upon the following 
considerations : 

In granular atrophy of the kidneys large tracts of renal paren- 
chyma are destroyed, the result being a diminution in the area 



THE URINE. 281 

of glandular material, which in itself could lead to a diminished 
secretion of urine. The coexisting cardiac hypertrophy, how- 
ever, by raising the blood-pressure in the kidneys, is supposed to 
counterbalance the renal deficiency and even lead to an increase 
in the amount of urine. There seems to be some doubt as to the 
correctness of such an explanation, as the existence of hypertrophy 
of the left ventricle in the absence of glandular disease of the kid- 
neys by no means leads to a degree of polyuria at all comparable to 
that observed in this disease. It is possible that while cardiac 
hypertrophy in itself may be one of the causative factors, still 
another may be vicarious action of the sound glandular elements. 
If such be the correct explanation, the coexisting polydipsia is 
merely secondary. This, however, can be regarded only as an 
hypothesis, and the diminished renal secretion associated with a 
gradually developing cardiac dilatation cannot be upheld as an 
absolute proof of its correctness. 

Polyuria, furthermore, lias been observed in the most diverse 
diseases of the nervous system, both functional and organic, illus- 
trating the influence of the nerve-centres upon renal activity, 
leaving the ultimate cause an open question. It is thus frequently 
observed both as a transitory and a permnent symptom in cases of 
hysteria. Large quantities of a very pale urine are secreted after 
the occurrence of severe hysterical seizures, but the same may be 
observed throughout the course of the disease. A similar condition 
is frequently seen in neurasthenia, migraine, chorea, and epilepsy. 

On the whole, it may be said that a paroxysmal polyuria in 
nervous diseases is associated with functional derangements, while 
a continuous polyuria appears to be connected rather with true 
organic changes. It has been observed in certain cases of tabes, 
cerebro-spinal and spinal meningitis, the first stage of general paresis, 
tumors affecting the medulla, the cerebellum, and spinal cord, in 
injuries affecting the central nervous system, in Basedow's dis- 
ease, etc. 

Cases of idiopathic diabetes insipidus most probably must be 
classified under this heading; enormous quantities of urine may be 
secreted in this disease, being equalled only by cases of diabetes 
mellitus, and at times reaching 43 liters per diem. 

Oliguria. Oliguria is, on the whole, more frequent than poly- 
uria, being met with in almost all conditions associated with a low- 
ered blood-pressure. First in order stand those cases of cardiac 



282 CLINICAL DIAGNOSIS. 

disease in which compensation has failed, whether the cardiac weak- 
ness be primary or occurring secondarily to other diseases — i. e., 
pulmonary, hepatic, and renal. 

The oliguria observed in the so-called continued fevers, notably 
typhoid fever, is probably also referable to the existence of cardiac 
weakness. It should be remembered, however, that a larger pro- 
portion of water is eliminated through the skin and lungs than 
normally, and that a retention of fluids also undoubtedly occurs in 
fevers, not referable to cardiac weakness, while still other factors 
may be concerned in its production. 

The oliguria occurring in acute nephritis and in chronic paren- 
chymatous nephritis in all probability depends largely upon mechan- 
ical causes, the increased intra-canalicular resistance iu the form of 
desquamated epithelium and tube-casts, as well as the pressure of 
the exudate upon the bloodvessels obstructing the passage of urine, 
while the functional activity of the diseased glandular elements is 
at the same time lowered. 

Upon mechanical causes, also, depend all those cases of oliguria 
associated with the presence of a stone or tumor, which pressing 
upon any part of the urinary tract impedes the flow of urine. Oli- 
guria may occur as a nervous manifestation in connection with 
puerperal eclampsia, lead-colic, hysteria, psychic depressions, pre- 
ceding and during epileptic seizures, etc. Whenever there is a 
diminution in the amount of bodily-fluids oliguria is also observed. 
this being particularly marked in cholera and following severe 
hemorrhages. <* 

Obstruction to the flow of blood in the vena cava or liver, lead- 
ing to an increase of venous pressure and a decrease of arterial 
pressure in the kidneys, likewise results in oliguria, as is seen in 
atrophic hepatic cirrhosis, acute yellow atrophy, thrombosis of the 
vena cava and the renal vein, or in case- in which pressure is 
exerted upon these by tumors, ascitic fluid, etc. 

In anv case the oliguria may go on to complete anuria, which 
condition not infrequently precedes death. Anuria may. however, 
also occur independently of a pre-existing oliguria, notably so in 
cases of hysteria. 

Specific Gravity. 

The specific gravity of normal urine varies between 1.015 and 
1.025, corresponding to 1200 to 1500 c.c, the normal amount of 



THE URINE. 283 

urine voided in twenty-four hours. Pathologically a specific 
gravity of 1.002 on the one hand and 1.060 on the other may 
occur, depending upon the amount of solids and fluids present, 
increasing as the solids increase, the amount of urine remaining 
the same, and decreasing as the amount of fluid increases, the 
solids remaining the same. The specific gravity is thus an index, 
in a general way, of the metabolic processes taking place in the 
body. 

The necessity of determining the specific gravity of the total 
amount of urine voided in a given case, and not that of an indi- 
vidual specimen passed during the twenty-four hours, becomes 
apparent upon considering the variations which can occur in the 
solids and liquids during the day. The ingestion of large amounts 
of water or beer would, of course, result in the passage of a corre- 
spondingly large quantity of urine within the next few hours, con- 
taining but a small amount of solids, and hence presenting a low 
specific gravity. It would be erroneous to infer a diminished 
excretion of solids for the day from such an observation, as suc- 
ceeding specimens would in all probability be passed presenting a 
higher specific gravity. An observation, moreover, made upon a 
specimen taken from the collected quantity of urine of the twenty- 
four hours can only then convey a correct idea if the quantity falls 
within the normal limits. If this should not be the case, the 
volume of urine observed must first be reduced to the normal and 
the specific gravity then taken. 

Supposing a known quantity of common salt to be dissolved in 
1000 c.c. of water, so that the resulting specific gravity be 1.24, 
by doubling the amount of salt and water the specific gravity 
would still remain the same, while the amount of salt would actu- 
ally be twice as large as at first. In order to obtain the specific 
gravity indicating the true amount of solids present it would be 
necessary to concentrate the fluid to 1000 c.c. The specific gravity 
being inversely proportionate to the amount of fluid secreted, the 
necessary correction is made according to the following formula : 

Sp.gr. =% 

in which Sp. gr. indicates the specific gravity to be determined, 
q the amount of urine actually passed, d the specific gravity 
observed, and N the normal amount of urine — i. e., 1200 c.c. 

Example : A patient has passed 3000 c.c. of urine in the twenty- 



284 CLINICAL DIAGNOSIS. 

four hours with a specific gravity of 1.017; this is corrected accord- 
ing to the above formula: 

Sp.gr. =?? 00 X 1 J= 1.042. 
F 5 1200 

From the specific gravity the amount of solids can be calculated 
with sufficient accuracy for clinical purposes by multiplying the 
last two decimal points by 2, the number obtained indicating the 
amount of solids in 1000 c.c. of urine. 

To illustrate the necessity of either indicating the total amount 
of urine passed within the twenty-four hours, and of taking the 
specific gravity from this collected urine, or of correcting the 
specific gravity as shown above (which latter method is far prefer- 
able, and should be generally adopted in urinary reports), the fol- 
lowing case may be supposed: 

A "specimen" of urine is taken from a man, presenting a 
specific gravity of 1.002; by multiplying the 2 by 2, the person 
would be supposed to pass 4 grammes of solids in every 1000 c.c. 
of urine. Had the specific gravity been observed in the total 
amount of urine passed in the same twenty-four hours, it would 
have been found to be 1.012, the man having passed 3000 c.c. of 
urine; by multiplying 12 by 2, 24 grammes of solids would have 
represented the amount in every 1000 c.c. — i. e., 24X3 = 72 
grammes in toto. The same result would have been reached by 
correcting the specific gravity of 1.012 for the normal amount of 
urine. 

The first calculation then would have indicated a considerable 
deficit as compared with the second. 

The following rules for practice may thus be stated : 

1. Whenever the specific gravity only is to be indicated in a 
urinary report it should always be the corrected one; if this is not 
done, the amount of urine should be stated in every case. 

2. The specific gravity should always be taken from a specimen 
of the collected urine of the tw T enty-four hours, and never from a 
specimen ad libitum. 

From" the rule that the specific gravity of a urine is inversely 
proportionate to the amount of fluid eliminated it must follow that 
whatever causes produce oliguria will also produce a high specific 
gravity, while all those causes which will produce a polyuria will 
similarly produce a low specific gravity, with the following excep- 
tions: 



THE URINE. 



285 



1. A diminished amount of urine with a Lowered specific gravity 
occurs in many chronic diseases and toward the fatal termination 

of acute diseases, indicating a defective elimination of solids. 
'2. The same may be observed in certain cases of oedema. 

3. Following copious diarrhoea, vomiting, and sweating. 

4. A high specific gravity is associ- 
ated with polyuria in diabetes mellitus. 

Unfortunately the determination of 
the specific gravity and the solids con- 
tained in urines does not furnish as 
valuable information in many cases as 
would be a priori expected, organic 
constituents in general being possessed 
of a lower specific gravity than the in- 
organic, among which the chlorides are 
especially important, as they occur in 
considerable amount in normal urine. 
It thus not infrequently happens that 
the nitrogenous constituents are consid- 
erably increased, while the specific 
gravity is relatively low, owing to the 
absence or a diminution in the amount 
of chlorides. In other words, while 
the specific gravity may be regarded 
as a fair index of the total amount of 
solids excreted, its increase or decrease 
furnishes no information as to the na- 
ture of the constituents causing such a 
change. 

Determination of the Specific 
Gravity. The specific gravity of 
urine is most conveniently determined 
by means of a hydrometer indicating 
degrees varying from 1.002 to 1.040. Such instruments constructed 
especially for the examination of urine are termed urinometers (Fig. 
74). A good instrument should have a stem upon which the in- 
dividual divisions are at least 1.5] mm. apart, and in which each 
division should correspond to a half degree. 

Urinometers may also be purchased which are provided with a 
thermometer, a matter of great convenience. Every instrument 




Urinometer. (W. Simon.) 



286 



CLINICAL DIAGNOSIS. 



should be carefully tested by comparison with a standard hydrom- 
eter. 

In order to determine the specific gravity in a given case a cylin- 
drical vessel is nearly filled with urine and the urinometer slowly 
inserted, the reading being taken at the lower meniscus by bringing 
the eye on a level with it as soon as the instrument has come to a rest. 

Precautions. 1. The urinometer must be given ample room, and 
the reading should never be taken when the instrument adheres 
to the sides of the vessel, as owing to capillary attraction it is other- 
wise raised, causing the reading to become too high. 

2. The instrument must be perfectly dry and clean before being 
used, and should never be allowed to "drop" into the urine, as 
otherwise the weight of the instrument being increased by adhering 
drops of water, the reading becomes too low. 

3. Any foam upon the surface of the urine should first be re- 
moved by means of a piece of filter-paper, as it interferes with the 
accuracy of the reading; bubbles of air adhering to the instrument, 
thereby raising it, should be carefully removed with a feather. 



Fig. 75. 




The pyknometer. 



4. The specific gravity should always be determined in specimens 
taken from the twenty-four-hour urine, and corrected according to 
the formula given above. 

5. If the quantity of urine is too small to determine its specific 
gravity with a urinometer, the following method may be advan- 
tageously employed: 



THE URINE. 



287 



About 50 e.c. of uriae are measured off, preferably by means of 
a burette, into a small bottle provided with a ground-glass stopper 
or into a pyknometer like the one pictured in Fig. 75, and accu- 
rately weighed. The weight of the urine divided by its volume 
gives the specific gravity, which must, however, be corrected for 
the temperature of the urine. If accuracy be required, such a cor- 
rection should be made in every case, as the specific gravity increases 
or decreases by 1° for every 3° C. above or below the point for which 
the instrument is registered, viz., 15° C. According to Bouchardat 
and Mercier, this method is not strictly accurate, and the following 
table has been constructed by which the proper corrections can 
readily be made: 



empera- 


Urine 


Glycosuric 


Tempera- 


Urine 


Glycosuric 


ture. 


normal. 


urine. 


ture. 


normal. 


urine. 


0° 


0.9 


1.3 


18° 


0.3 


0.6 


1 


0.9 


1.3 


19 


0.5 


0.8 


o 


0.9 


1.3 


20 


0.9 


1.0 


3 


0.9 


1.3 


21 


0.9 


1.2 


4 


0.9 


1.3 


6 22 


1.1 


1.4 


5 


0.9 


1.3 


23 


1.3 


1.6 


6 


0.8 


1.2 


24 


1.5 


1.9 


7 


0.8 


1.1 


25 


1.7 


2.2 


8 


0.7 


1.0 


26 


2.0 


2.5 


9 


0.6 


0.9 


27 


* 2.3 


2.8 


10 


0.5 


0.8 


28 


2.5 


3.1 


11 


0.4 


0.7 


29 


2.7 


3.4 


12 


0.3 


0.6 


30 


3.0 


3.7 


13 


0.2 


0.4 


31 


3.3 


4.0 


14 


0.1 


0.2 


32 


3.6 


4.3 


15 


0.0 


0.0 


33 


3.9 


4.7 


16 


0.1 


0.2 


34 


4.2 


5.1 


17 


0.2 


0.4 


35 


4.6 


5.5 



Example: Supposing the specific gravity to have been 1.030 at a 
temperature of 20° C, it would be necessary to add 0.9 to the 1.030, 
making this 1.0309; at a temperature of 10° C, it would similarly 
be necessary to subtract 0.5. 

Determination of the Solid Constituents. As indicated above, 
the amount of solids can be calculated with a degree of accuracy 
sufficient for clinical purposes by multiplying the last two figures 
of the specific gravity by 2, the number obtained indicating the 
amount of solids in every 1000 c.c. of urine. If greater accuracy 
be required, the following method may be employed: 

Five c.c. of urine, accurately measured, are placed in a watch- 



288 CLINICAL DIAGNOSIS. 

crystal containing a little dry sand (sand and crystal having been 
previously weighed): this is placed over a dish containing concen- 
trated sulphuric acid, and under the receiver of an air-pump. 
which has been made perfectly air-tight by thoroughly lubricating 
the ground-glass edge of the bell with mutton tallow and apply- 
ing the bell with a slightly grinding movement to the ground- 
glass plate. The receiver is now exhausted and the urine allowed 
to remain in the vacuum for twenty-four hours, when the bell is 
again exhausted and left for twenty-four hours longer; at the end 
of this time the crystal is weighed, the difference between the two 
weights obtained indicating the amount of solids in 5 c.c. of urine, 
from which the percentage and total amount are readily calculated. 
The slight loss of ammonia which results when this method is 
employed scarcely affects the accuracy of the result. 

REACTION. 

The reaction of the twenty«-four-hour urine is, as a rule, acid; 
individual specimens, passed in the course of twenty-four hours, 
may be either alkaline, acid, or amphoteric. 

When a mixture of several different acids is brought into contact 
with a mixture of* alkalies, the acids combine with the alkalies 
according to the degree of affinity which exists between the two 
and the amount present of each. Upon the excess of acids over 
alkalies, and vice versa, depends the resulting reaction. If the 
alkalies are not sufficient in amount to saturate the acids, an acid 
reaction will result, while an insufficient amount of acid will give 
rise to an alkaline reaction. The same principle holds good for 
the acids and alkalies giving rise to the salts present in the urine. 
As here the alkaline substances are not present in sufficient amount 
:: saturate the acids, which can readily be seen from the following 
table, the acid reaction of normal urine is explained: 



hq 


si 


PA 


K 


X9a 


EHj 


Ca 


Mg 


10.13 ' 
S.3811 


2.3157 
1.3315 


3.0334 


1.5194 


i £ 

■ m 


" 


0.0405 
0.0233 


O.OSi 

0.0843 



The fig tires in the first column indicate the average dailv amount 
of the inorganic acids and alkalies present in the urine of twenty- 
four hours, and the figures in the second column their equivalents 






THE URINE. -JM) 

in term- of \a, that of P.O. having been estimated as NaH 2 P0 4 , 
From this it is seen that the acid equivalents, 8.6953, exceed the 
alkaline equivalents, 7.9137, by 0.7816 gramme of Na. There 
are present then in the urine, in addition to the normal salts of the 
monobasic acids, acid -alts and especially diacid sodium phosphate, 
XaH 2 P0 4 . To the latter the acidity of the nrine is due. If, on 
the other hand, the alkalies exceed the acids in amount, an alkaline 
urine will result, which may occur physiologically under various 
conditions. 

The so-called amphoteric reaction may be observed at times when 
the diacid and neutral sodium phosphates, !S T aH 2 P0 4 and Na 2 HP0 4 , 
are present in a certain definite proportion, the urine changing the 
color of red litmus-paper to blue, and vice versa. 

A neutral urine is never observed under normal conditions. 
Moreover, the presence of a free acid is not possible, as it would 
immediately cause the formation of ammonia from the tissues of 
the body, and, finally, the urea in the urine would combine with 
any free acid which might be present. 

The question now arises, Whence does the acidity of the urine 
result, and what are the ultimate causes which will produce an alka- 
line and an amphoteric reaction ? 

These are problems which as yet await a final decision. Our 
present ideas, however, may be formulated as follows: In the 
metabolism of the body-tissues acids are constantly produced, chief 
among these being sulphuric acid, resulting from albuminous de- 
composition, and hydrochloric acid, which at a certain period of 
digestion is reabsorbed into the blood together with peptones. As 
the alkalinity of the blood is due to neutral sodium phosphate and 
sodium carbonate, these salts are attacked by the free acids as soon 
as they enter the blood, the result being the formation of acid salts, 
and, as the latter diffuse more readily through an animal membrane 
than alkaline salts, the secretion of an acid urine from the alkaline 
blood is in part explained. 

Nevertheless, it is impossible to exclude a certain specific action 
on the part of the glandular elements of the kidneys, as otherwise 
the secretion of all glands, supposing this to depend upon a process 
of filtration or diffusion only, would necessarily be acid. 

As the alkalinity of the blood increases the acidity of the urine 
decreases, until finally an alkaline urine results. The degree of 
the alkalinity of the blood, however, depends essentially upon the 

19 



290 CLINICAL DIAGNOSIS. 

nature of the food and the secretion of the gastric juice, viz., hydro- 
chloric acid. The ingestion of vegetable food rich in salts of organic 
acids, which become oxidized in the body to the carbonates of the 
alkalies, will result in the passage of an alkaline urine, as the alka- 
lies thus formed when absorbed into the blood are more than suffi- 
cient to neutralize completely all the acids present, the elimination 
of neutral sodium phosphate alone taking place. In the case of 
animal food the reverse holds good. The alkaline carbonates here 
formed not being sufficient to neutralize the excess of acids, diacid 
phosphate of sodium is eliminated in large quantity. 

An amphoteric urine results whenever the elimination of neutral 
and acid sodium phosphate is equal; such an occurrence must, there- 
fore, be regarded as being more or less an accident. 

As the alkalinity of the blood is increased during the secretion of 
the acid gastric juice, it may frequently happen, especially following 
the iugestion of a large amount of food, that an alkaline urine is 
voided. If this does not take place, the acidity of the urine is at 
least diminished, to increase again during the process of resorption 
of hydrochloric acid and peptones. The statement so generally 
made in text-books, that the urine secreted after a meal is alkaline, 
is not strictly correct; in a series of observations made by the author 
upon human subjects an alkaline urine was observed in only 20 per 
cent, of the cases examined. 

It may then be stated that an alkaline urine will result under 
physiologic conditions whenever the alkaline salts present in the 
food are sufficient to neutralize all the acids formed, as occurs in 
the case of a vegetable diet, and, furthermore, whenever the period 
of gastric secretion is lengthened. 

If an acid urine be allowed to stand exposed to the air for a cer- 
tain length of time, its degree of acidity gradually diminishes, the 
reaction finally becoming alkaline. At the same time the urine 
becomes cloudy and deposits a sediment, consisting of ammonio- 
magnesium phosphate, MgNH 4 P0 4 -j- 6H 2 0, neutral calcium phos- 
phate, Ca 3 (P0 4 ) 2 , and still later of ammonium urate, C 5 H 2 (NH 4 ) 2 ]Sr 4 Og, 
in addition to the constituents of the primitive nubecula — i. e., a few 
mucous corpuscles and pavement epithelial cells. The entire volume 
of urine, moreover, remains cloudy, owing to the presence of innu- 
merable bacteria. The odor becomes extremely disagreeable, and 
distinctly "urinous." In short, " ammoniacal decomposition " 
has occurred. This has been shown to depend upon the action 



THE URINE. 291 

of certain bacteria, notably the micrococcus urese and the bacterium 
urese, present in the air, these organisms causing the decomposition 

of the urea found in every urine, with the formation of ammonium 
carbonate, according to the following equation: 

CO(NH 2 \> + 2H 2 = (NH 4 ) 2 C0 3 
(NH 4 * 2 CO s = 2NH 3 + H 2 + C0 2 . 

Here as elsewhere, however, it is not the bacterium which directly 
produces the result, but a bacterial product, and in this case an 
enzyme. 

An alkaline urine, the akalinity, however, not being due to 
ammoniacal fermentation, but to causes already mentioned, may, 
of course, undergo the same change as an acid urine; but it is neces- 
sary to distinguish sharply between these two varieties of alkaline 
urines, the recognition of the cause of the alkalinity being very 
often most important in diagnosis. The distinction is readily made 
by fastening a piece of sensitive red litmus-paper in the cork of the 
bottle containing the urine. If the alkalinity of the urine be due 
to the presence of ammonia, the litmus-paper will turn blue, but 
soon changes to red again when exposed to the air; w T hile a urine, 
the alkalinity of which is due to the presence of fixed alkalies, will 
turn red litmus-paper blue only when immersed directly in the urine, 
the change in color at the same time persisting. 

As ammoniacal decomposition can also occur within the urinary 
passages, it is important whenever an alkaline reaction due to 
the presence of ammonia is observed to test the urine at once upon 
being voided, or, still better, to procure a portion with the catheter. 
Such urines are frequently seen in cases of cystitis the result of 
paralysis, urethral stricture, gonorrhoea, etc. 

An intensely acid reaction is observed in almost all concentrated 
urines, especially in fevers, in certain diseases of the stomach asso- 
ciated with a diminished or suspended secretion of hydrochloric 
acid, in gout, lithiasis, acute articular rheumatism, chronic Bright' s 
disease, diabetes, leukaemia, scurvy, etc. Whenever a very acid 
urine is secreted for a considerable length of time the possibility of 
renal irritation and the formation of concretions should be borne in 
mind. 

An alkaline urine, the alkalinity of which is not owing to the 
presence of ammonia, but to a fixed alkali, is observed in certain 
cases of debility, especially in the various forms of anaemia, follow- 
ing the resorption of alkaline transudates, the transfusion of blood, 



292 CLINICAL DIAGNOSIS. 

frequent vomiting, a prolonged cold bath, etc. It may also be 
due to the ingestion of certain medicines, viz., salts of the organic 
acids and alkaline carbonates, the former being transformed into 
the latter, as has been mentioned. An increase in the degree of 
acidity may similarly take place after the ingestion of mineral 
acids. 

It is apparent then that an increase or a decrease in the acidity 
of the urine cannot be immediately attributed to a certain disease. 
Conclusions can only be drawn if all other causes, both physiologic 
and pathologic, can be eliminated. 

Determination of the Acidity of the Urine. The old method 
of titrating a certain amount of urine with a decinormal solution of 
sodium hydrate has now been abandoned and replaced by that of 
Freund. This is essentially based upon the observation that the 
acid reaction of the urine is referable exclusively to diacid phos- 
phates. 

FreuncVs method. In 50 c.c. of urine the total amount of phos- 
phoric acid is estimated as described on p. 312. The result is termed 
T. In a second portion of 50 c.c. the monacid phosphates M are 
then precipitated with a normal solution of barium chloride — i. e., 
one containing 122 grammes of the crystallized salt in 1000 c.c. of 
water — 10 c.c. being added for every 100 mgrms. of the total 
amount of phosphoric acid found. After the addition of the barium 
the mixture is diluted to 100 c.c, filtered, and the phosphoric acid 
estimated in 50 c.c. of the filtrate. The result obtained is termed 
D. Owing to the fact that the monophosphates are not only pre- 
cipitated upon the addition of the barium chloride, but also a small 
amount of normal phosphates, and that a small amount of diacid 
phosphate is formed at the same time and passes into solution, an 
error is thus incurred. This, however, remains constant, and amounts 
to 3 per cent, in favor of the diacid phosphates. As the total amount 
of phosphoric acid is subject to fairly wide variations, even in health, 
being increased especially after meals, it is best to calculate the rela- 
tive proportion of T to D for 100 c.c. of urine, and then to deter- 
mine the absolute degree of acidity for the twenty-four hours. Fig- 
ures are thus obtained which are directly comparable with oue an- 
other. 

Example: Supposing that T amounted to 0.386 gramme for 100 
c.c. of urine, and D to 0.338 gramme. Three per cent, of D would 
then have to be deducted for reasons just given, and added to M, 



the urim:. 293 



ma 



king the true value of 1) 0.3368. The relative proportion of T 
to I> would then be 87.5, as determined according to the equation : 

0.3S6 : 0.3308 : : 100 : x, and x = 87.5. 

Supposing, further, that the total amount of urine was 2000 c.c., 
the total acidity for the twenty-four hours would correspond to 1740, 
according to the equation 100 : 87.5 : : 2000 : x, and x = 1740, and 

the total acidity per hour to , i. e., 72.5. 

The results obtained can also be expressed in terms of hydro- 
chloric acid, 100 mgrms. of the diacid phosphates corresponding to 
102.8 mgrms. of hydrochloric acid. This mode of indicating the 
total acidity of the urine would actually be the better. If the urine 
should be alkaline and cloudy, the sediment is first dissolved by 
carefully adding a one-tenth or one-fourth normal'solution of hydro- 
chloric acid, the amount added being then deducted from the total 
acidity. Should negative values be found, these could be expressed 
in terms of sodium hydrate. 1 

With this method a complete revision of all the work previously 
accomplished will be necessary, and the results given above have 
reference only to the old method of titration with a one-tenth nor- 
mal solution of sodium hydrate. 

An increase in the acidity of the urine upon standing has been 
repeatedly observed, and is probably due to the formation of new 
aeids from pre-existing acid-yielding substances, such as certain 
carbohydrates, alcohol, etc., which have undergone fermentation. 
This phenomenon is frequently observed in the urine of diabetic 
patients. 

A decrease in the acidity of normal urine upon standing is, on the 
other hand, the rule, owing to decomposition of urate of sodium by 
the acid phosphate of sodium, acid urate of sodium and, later on, 
uric acid resulting, which are thrown down as a sediment in conse- 
quence of the diminished acidity of the urine, and which, hence, 
no longer influences its reaction. This is shown in the equations: 

T. NaHjPO* + C 5 H 2 Xa 2 X 4 3 = Na 2 HP0 4 + C 5 H 3 NaN 4 3 
II. XaH 2 P0 4 + C 5 H 3 Na N 4 3 = Na 2 HP0 4 -f- C 5 H 4 N 4 3 



1 The urine is carefully guarded against ammoniacal decomposition by the addition to the 
first portion voided of from 20 to 25 c.c. of a solution of 10 grammes of oil of peppermint in 100 
c.c. of alcohol. 



294 



CLIXICAL DIAGNOSIS. 



THE CHEMISTRY OF THE URINE. 

G-eneral Chemical Composition of the Urine. It has been 
pointed out that, owing to the influence exerted upon the chemical 
composition of the urine by many factors, such as age, sex, tem- 
perature, digestion, exercise, etc., the figures given by different 
observers to express the absolute quantities of the various ingre- 
dients eliminated in the twenty-four hours vary within fairly wide 
limits. A general idea may, however, be formed of these constitu- 
ents, and their average amounts under physiologic conditions, from 
the following table: 



Composition' of Normal Huma 
Gravity, 



Urixe of Average Specific 
e, 1.020. 1 



Per liter. Per 24 hours. 

Water 956 grms. 1243 grms. 

Organic matter .... 28-30 " 36-38 " 

Urea 25.37 " 33.00 " 

Uric acid . . . . ■ 0.40 grm. 0.52 grm. 

Hippuric acid . . . . 0.50 " 0.65 " 

Creatin and creatinin . . 0.80 " 1.0 " 

Xanthin bases . . . . 0.04 " 0.052" 

Coloring-matter and extractives 4.5 grms. 5.850 grms. 

Volatile fatty acids . 

Oxalic acid 

Phenol sulphate 

Indoxyl and skatoxyl sulphate 

Paraoxyphenylacetic acid . ]- Very little. 

Sugar .... 

Mucus, pepsin . 

Fatty acids 

Glycerine-phosphoric acid 
Mineral matter . . . 16-17 grms. 

Sodium chloride . . . 10.5 " 

Alkaline sulphates . . . 3.1 " 

Earthy phosphates . . . 0.76 grm. 

Alkaline phospnates . . 1.43 " 

Silicic acid .... 
Nitric acid . . . • • > Traces. 
Gases (0,C0 2 ,N) 

In pathologic conditions the following substances may also be 
found in solution: Albumin, globulin, hemialbumose, peptone, 
mucin (nucleo-albumin), glucose, lactose, inosit, dextrin, biliary 
constituents, viz., bile-acids and bile-pigments, blood-pigment, 



20-21 | 

13.65 

4.03 



0.98 grm. 
1.86 " 



i Taken from Gamier. 



THE URINE. 



295 



urorubrohsematm, urorubrofuscin, melanin, leucin, tyrosin, oxy- 
butyric acid, allantoin, fat, lecithin, cholesterin, acetone, alcohol, 
Baumstark's substance, arocaninic acid, cystin, and sulphuretted 
hydrogen. 

Quantitative Estimation of the Mineral Ash of the Urine. 
In order to estimate the amount of mineral ash in the urine the 
following method may be employed: 

Fifty c.c. of urine are evaporated to dryness in a weighed porce- 
lain dish at a temperature of 100° C, and then heated, while covered, 
over the free flame until gases cease to be evolved, care being taken 
not to heat too strongly in order to prevent sputtering. The residue 

Fig. 76. 




Desiccator. (W. Simon.) 

is taken up with distilled boiling water, and, after standing, filtered 
through a Schleich and SchihTs filter, the weight of the ash contained 
in this being known. The dish and the contents of the filter are 
well washed with hot water. Filtrate and washings are set aside and 
the dish and filter dried in the oven at 115° C. The filter is now 
placed in the dish and slowly incinerated. As soon as the ash has 
turned white the filtrate and washings are placed in the same dish, 
evaporated at 100° C, and then carefully heated over the free flame. 
Upon cooling in the desiccator (Fig. 7d) the dish with its contents 
is weighed, the difference between its present and previous weight 
indicating the quantity of ash contained in 50 c.c. of urine. 

Precautions: 1. Care should be taken to allow the dish to become 
faintly red only for a moment, since some of the chlorine is other- 
wise volatilized. Some phosphoric acid also may be volatilized, 
and too strong a heat, moreover, may cause the transformation of 



296 CLINICAL DIAGNOSIS. 

sulphates into sulphides, the organic material present acting as a 
reducing agent. 

2. If the organic ash is not completely incinerated, it is best to 
allow the dish to cool and then to moisten the ash with a few drops 
of distilled water, it being thereby brought into closer contact with 
the surface of the dish. 

The Chlorides. 

The chlorides excreted in the urine are derived from the food. 
As they are thus present in a much larger amount than all other 
inorganic salts combined, and in quantity more than sufficient to 
supply the needs of the body-economy, the relatively large amount 
of chlorides found in the urine under physiologic conditions, as com- 
pared with the other inorganic constituents, is readily explained. 

Of the alkalies in the urine, sodium in combination with chlorine 
exists in greatest amount, and for clinical purposes it is most con- 
venient to calculate the total quantity of chlorides found in terms 
of sodium chloride; a small proportion of chlorine also occurs com- 
bined with potassium, ammonium, calcium, and magnesium. 

From 11 to 15 grammes of sodium chloride, representing the 
total quantity of chlorine, are normally eliminated in the twenty- 
four hours, the amount depending, of course, directly upon that 
contained in the food ingested. If the amount of nourishment is 
diminished, a decrease in the elimination of the chlorides is observed. 
If this be carried to the point of starvation, the chlorides disappear 
almost entirely from the urine, the traces remaining being derived 
from the body-fluids. The latter retain tenaciously a certain 
amount, which differs but slightly from that normally present. If 
at this stage food containing sodium chloride is again taken, a por- 
tion will be retained in the body until the original equilibrium is 
restored. A similar retention may be observed for a few days 
following the ingestion of large quantities of water, which causes 
an increased elimination of chlorides. 

This tenacity on the part of the body in retaining sodium chlo- 
ride is strikingly seen when the potassium salt is substituted for 
the sodium salt; in this case the amount of the sodium in the serum 
of the blood will be found to vary but very slightly. 

It has also been shown that the excretion of sodium chloride 
can be very materially increased by the ingestion of potassium 
salts, notably the neutral potassium phosphate (K 2 HPOJ. This is 



THE URINE. 297 

supposed to decompose the sodium chloride present in the serum, 
resulting in the formation of potassium chloride and neutral sodium 
phosphate, which are both eliminated from the body as foreign 
matters ; a point is finally reached, however, when the sodium 
chloride ceases to be excreted. 

This provision of the economy, in virtue of which an increase in 
the elimination of the salt is followed by its retention, and a pre- 
vious retention by an increased elimination, is supposed to be refer- 
able to the albuminous metabolism taking place in the body. It 
may be stated, as a general rule, that any increase in the amount of 
circulating albumin will be followed by an elimination of chlorides, 
these haviug been previously retained by the albuminous bodies in 
consequence of the great affinity which exists between them. At 
the same time the elimination of chlorides is influenced by the 
quantity of urine excreted, increasing and decreasing with its 
volume. 

Pathologically the excretion of the chlorides may vary within 
wide limits, diminishing on the one hand to zero, and increasing 
on the other to as much as 50 grammes or more in the twenty-four 
hours. A marked diminution, going on in some cases to a total 
absence of the chlorides, was formerly thought to be pathognomonic 
of acute croupous pneumonia. Recent investigations, however, have 
shown that such a condition is present to a greater or less degree in 
most acute febrile diseases, such as scarlatina, roseola, variola, typhus 
and typhoid fevers, recurrens, and acute yellow atrophy. 

The explanation of this phenomenon must be sought for, first, in 
a diminished ingestion of chlorides; secondly, in a retention of these 
in the blood, probably associated with an increase in the amount 
of circulating albumin; thirdly, in a diminished reual secretion of 
water; fourthly, in a possible elimination of a portion of the chlo- 
rides from the blood by other channels, as in cases of severe diar- 
rhoea, the formation of serous exudates, etc. Intermittent fever 
appears to be an exception to this rule; the chlorides, it is true, 
are usually diminished, but not to the extent seen in the other dis- 
eases mentioned; they have, moreover, been found to increase during 
and sometimes immediately after a paroxysm, this increase being, of 
course, followed by a corresponding decrease. 

The chlorides are diminished in all acute and chronic renal dis- 
eases associated with albuminuria, owing, to some extent, at least, 
to a diminished secretion of water. In all cases of carcinoma of 



298 CLINICAL DIAGNOSIS. 

the stoma ch, chronic hypersecretion of gastric juice, associated with 
dilatation, a decrease is also observed, which in certain cases of 
hypersecretion and hyperacidity the result of gastric ulcer may go 
on to a total absence. In ansemic conditions the chlorides are like- 
wise diminished, as also in rickets. In melancholia and idiocy a 
striking decrease is observed; in dementia, chorea, and pseudo- 
hypertrophic paralys : s this is less marked. A total absence has 
been noted in pemphigus foliaceus, and a considerable diminution 
in the beginning of imj^etigo, as also in chronic lead-poisoning. 

The chlorides are found in increased amount, on the other hand, 
in all conditions in which retention has previously occurred, chief 
among these being the acute febrile diseases and cases in which a 
resorption of exudates and transudates, associated with an increased 
diuresis, is taking place. A marked increase has also been noted 
in some cases of diabetes insipidus, in which 29 grammes of sodium 
chloride have been eliminated in the twenty-four hours. A similar 
increase may occur in prurigo, in which, in one instance, 29.6 
grammes were passed in twenty-four hours. In cases of general 
paresis during the first stage an increased elimination goes hand 
in hand with an increased ingestion of food. In epilepsy the polyuria 
following the attacks is associated with an increase in the chlorides. 

Of drugs, certain diuretics, and some of the potassium salts, as 
has been mentioned, produce an increase: the chlorine contained in 
chloroform, whether administered internally or as an anaesther::. ie 
in part excreted in the form of a chloride. Salicylic acid, on the 
other hand, is said to cause a temporary diminution. 

It is of practical importance to note that in acute febrile affections 
the diminution in the chlorides appears to vary with the intensity 
of the disease, a decrease to 0.05 gramme pro dk justifying the 
conclusion that the case under observation is of extreme gravity. 
It may at times also indicate the previous occurrence of severe diar- 
rhoea or the formation of exudates of considerable extent. A con- 
tinued increase, on the other hand, should lead to the conclusion 
that the patient's condition is improving. 

The elimination of the chlorides also furnishes a fair index to the 
digestive powers of the patient. This rule also holds good for 
most chronic diseases. All other causes which might lead to an 
increase or decrease being eliminated, an excretion of from IX I 
15 grammes indicates a fair condition of the appetite and a normal 
digestive power, a decrease being associated with the reverse. 



THE URINE. 299 

An increased elimination of chlorides occurring in oases of oedema, 
and associated with the existence of serous exudates, is always of 
good prognostic significance, pointing to a resorption of the fluid. 

A continued elimination of more than lo to 20 grammes, all 
other causes being excluded, may be considered as pathognomonic 
of diabetes insipidus. 

Test for Chlorides in the Urine. The recognition of chlorides 
in the urine is based upon the fact that the addition of a solution 
of nitrate of silver causes their precipitation, the reaction taking 
place according to the following equation : 

AgN0 3 -f NaCl = AgCl +NaN0 3 . 

Silver chloride thus formed is insoluble in nitric acid. 

The test is made in the following manner: After having removed 
any albumin that may be present, according to methods given else- 
where (see Blood), a few c.c. of mine are acidified in a test-tube 
with about 10 drops of pure nitric acid, and a few c.c. of silver 
nitrate solution (1 : 20) added. The occurrence of a white precipi- 
tate indicates the presence of chlorides. An idea may be formed 
at the same time as to the quantity present, the occurrence of a 
heavy, caseous precipitate pointing to a large amount. 

Quantitative Estimation of the Chlorides by the Method of 

Salkowski-Volhard. When a solution of silver nitrate, acidified 

with nitric acid, is treated with a solution of potassium sulpho- 

cyauide or ammonium sulpho-cyanide in the presence of a ferric 

salt, the potassium sulpho-cyanide first causes the precipitation of 

white silver sulpho-cyanide, which, like silver chloride, is insoluble 

in nitric acid : 

AgN0 3 + KSCN =AgSCN + KN0 3 . 

As soon as every trace of silver is precipitated it combines with 
the ferric salt to form iron sulpho-cyanide, which is of a blood-red 
color, according to the equation: 

6KSCN + Fe 2 S0 4 ) 8 = Fe 2 SO T ) 6 + 3K 2 S0 4 . 

If the potassium sulpho-cyanide solution be of known strength, 
it is possible to estimate accurately the amount of silver present in 
the solution, the ferric salt serving as an indicator of the end of the 
reaction between the silver and the potassium sulpho-cyanide. 

Application to the urine : To urine which has been acidified with 
nitric acid an execs- of a silver solution of known strength is added, 
and the silver not used in the preciptation of the chlorides then esti- 



300 CLINICAL DIAGNOSIS. 

mated according to the method given above. The difference between 
the quantity thus found and the total amount used will be that con- 
sumed in the precipitation of the chlorides, from which, knowing 
the strength of the silver solution, its equivalent in terms of sodium 
chloride is readily determined. 
Reagents necessary: 

1. A solution of silver nitrate of such strength that every c.c. 
corresponds to 0.01 gramme of sodium chloride. 

2. A solution of potassium sulpho-cyanicle of such strength that 
25 c.c. correspond to 10 c.c. of the silver nitrate solution. 

3. A solution of a ferric salt, such as ammonio-ferric alum, 
saturated at an ordinary temperature. 

4. Xitric acid (specific gravity 1.2). 
Preparation of these solutions : 

1. As pointed out, the silver nitrate solution is made of such 
strength that every c.c. corresponds to 0.01 gramme of NaCl; in 
other words, a standard solution is employed. 

The silver nitrate to be used for this purpose must be pure, the 
crystallized salt being used and not the sticks wrapped in paper, 
which latter always contain reduced silver. In order to test the 
purity of the salt, about 1 gramme is dissolved in distilled water, 
heated to the boiling-point, the silver precipitated by dilute hydro- 
chloric acid and filtered off. The filtrate when evaporated in a 
platinum crucible should leave either no residue at all or only a 
very faint one; otherwise it is necessary to recrystallize the salt and 
test again, until the desired degree of purity is obtained. 

The determination of the quantity to be dissolved in 1000 c.c. 
of water is based upon the fact that one molecule of silver nitrate 
(molecular weight 170) combines with one molecule of sodium chlo- 
ride (molecular weight 58.5) to form silver chloride and sodium 
nitrate. As the solution of nitrate of silver shall be of such strength 
that 1 c.c. corresponds to 0.01 grm. of XaCl, or 1000 c.c. to 10 
grms., the quantity to be dissolved in 100 c.c. is found according 
to the following equation : 

58.5 : 170 : : 10 : x; 58.5 x=1700; x = 29.059. 

Theoretically, then, this quantity should be dissolved in 1000 c.c. 
of water. It is better, however, to dissolve this in a quantity some- 
what less than 1000 c.c, such as 900 or 950 c.c, as the silver salt 
may contain some water of crystallization and the weighed-off quan- 



THE URINE. 301 

tity not represent the accurate amount required, but less, the cor- 
recting of a solution which is too strong being a much simpler 
matter than that of a solution which is too weak. 

To make this correction, or, in other words, to bring the solution 
to its proper strength, 0.15 gramme of sodium chloride which has 
been previously dried carefully by heating in a platinum crucible, 
is accurately weighed off, dissolved in a little distilled water, and 
further diluted to about 100 cc. To this solution a few drops of 
a solution of chromate of potassium are added, and the mixture is 
titrated with that of silver nitrate. 

The nitrate of silver will first precipitate the sodium chloride 
present, and then combine with the potassium chromate, forming 
red silver chromate, according to the equation : 

2AgNO a + K 2 Cr0 4 = Ag,Cr0 4 + 2KN0 3 

The slightest orange tinge remaining after stirring indicates the 
end of the reaction. Were the solution of the silver nitrate of the 
proper strength, exactly 15 cc. should have been used, as every 
cc. represents 0.01 gramme of NaCl. As a matter of fact, less 
will in all probability be needed, the solution having been purposely 
made too strong. Its correction then becomes a simple matter, it 
merely being necessary to determine the degree of dilution required. 

Supposing the 29.059 grammes of silver nitrate to have been dis- 
solved in 900 cc of water, and that 14.5 cc instead of 15 cc 
had been required to precipitate the 0.15 gramme of sodium chlo- 
ride, it is evident that every 14.5 cc of the remaining solution 
must be diluted with 0.5 cc of water. It is, hence, only neces- 
sary to divide the number of cc. of the silver nitrate solution 
remaining by 14.5; the result multiplied by 0.5 represents the 
amount of water which must be added in order to bring the solu- 
tion to the required strength. Hence the rule for the correction of 
a solution which has been found too strong: 

n 

in wheh C represents the number of cc which must be added to 
the solution remaining; X the total number of cc remaining after 
titration; n the number of cc consumed in one titration; and d 
the difference between the number of cc theoretically required 
and that actually used in one titration. 

In the example given the equation would then read : 



302 CLINICAL DIAGNOSIS. 

c = 936.5 X 0-5 = 32 29 
14.5 

32.29 c.c. of distilled water are added to the remaining 936.5 c.c., 
and the strength of the solution tested by a second titration. If 
the solution be found too weak, it is best to make it too strong, and 
then to correct, as described. 

2. Preparation of the potassium sulpho-cyanide solution: From 
the equation AgN0 3 + KSCN = AgSCN + KN0 3 , it is seen that 
one molecule of silver nitrate (molecular weight 170) combines with 
one molecule of potassium sulpho-cyanide (molecular weight 97). 
The quantity of the latter to be dissolved in 1000 c.c. of water is 
thus found from the following equation: 

170 : 97 : : 11.6236 : x; 170 x = 11.6236 X 97 ; x = 6.6. 

As potassium sulpho-cyanide is extremely hygroscopic, a solution 
is made which is too strong by dissolving about 10 grammes of the 
salt in 900 c.c. of distilled water. In order to bring this solution 
to its proper strength, 10 c.c. of the silver nitrate solution are 
diluted to 100 c.c, 4 c.c. of nitric acid (specific gravity 1.2) and 
5 c.c. of the ammonio-ferric alum solution added, and the mixture 
titrated with the KSCN solution; the end-reaction is recognized by 
the production of a slightly reddish color, which persists on stirring. 
The KSCN solution having been purposely made too strong, it will 
be found that less than 25 c.c. will be needed in order to precipi- 
tate all the silver present. The quantity of water necessary for 
dilution is ascertained as above according to the formula: 

r, N. d 



3. The solution of ammonio-ferric alum is a solution saturated 
at ordinary temperatures, care being taken to insure the absence of 
chlorides in the salt, which may be effected, if necessary, by recrys- 
tallization. 

Method as applied to the urine: 10 c.c. of urine are placed in a 
small stoppered flask bearing a 100 c.c. mark, diluted with 50 c.c. 
of distilled water, and acidified with 4 c.c. of nitric acid. From 
a Mohr's burette 15 c.c. of the standard solution of silver nitrate 
are added. The mixture is thoroughly agitated and diluted with 
distilled water to the 100 c.c. mark. The silver chloride formed 
is filtered off through a dry folded filter into a dry graduate; 80 
c.c. of the filtrate are placed in a beaker, and, after the addition of 



THi: URINE. 303 

5 e.c. of the ammonio-ferric alum solution, titrated with the potas- 
sium sulpho-cyanide solution until the end-reaction — L e., a slightly 
reddish tinge — is seen. If necessary, two such titrations should be 
made, the potassium sulpho-cyanide solution being added 1 c.c. at a 
time in the first, while in the second the total number of c.c. needed 
to bring about the end-reaction, less 1 c.c, are added at once, and 
then one-tenth of a c.c. at a time. 

The amount of chlorides present in the urine is calculated as 
follows: 

Example : Total quantity of urine 600 c.c. ; 6.5 c.c. of the potas- 
sium sulpho-cyanide solution were required to bring about the end- 
reaction in 80 c.c. of the filtrate; this would correspond to 8.125 
c.c. for the total 100 c.c. of filtrate, representing 10 c.c. of urine, as 
is seen from the equation: 

n : 80 : : x : 100, 80 x = 100 n, x = 10 ° n = 5 - 11 , 

80 4 

in which x represents the number of c.c. corresponding to 100 c.c. 

of the filtrate, and n the number of c.c. actually used. 

These 8.125 c.c. were used in precipitating the remaining c.c. of 

the silver nitrate solution not decomposed by the chlorides. As 25 

e.c. of the potassium sulpho-cyanide solution correspond to 10 c.c. 

of the silver nitrate solution, the excess of silver solution in c.c. is 

found from the equation: 

ok in x- o= inv ION 2N 
2o : i0 : : is : x, 2o x — 10 N, x = = , 

25 5 

in which x represents the excess of silver nitrate solution in c.c, 
X that of the KSCN solution, as found in the equation above, x in 
this case being 3.25 c.c 

The differeuce between the total amount of silver solution em- 
ployed (i. e. y 15 c.c) and the excess (i. e., 3.25 c.c.) indicates, of 
course, the number of c.c necessary for the precipitation of the 
chlorides in 10 c.c of urine. In the case under consideration 
11.75 c.c. were employed. As 1 c.c of the silver solution repre- 
sents 0.01 gramme of NaCl, there must have been present in the 
10 c.c of urine 0.1175 gramme; in 100 c.c, hence, 1.175 grammes, 
and in the total amount — L e., 600 c.c of urine— 7.05 grammes. 

From these considerations the following short rule results: In- 
stead of first multiplying the number of c.c of the potassium sulpho- 
cyanide solution corresponding to 80 c.c. of the filtrate by J, as seen 
from the equation above, and the result by f, in order to find the 



304 CLINICAL DIAGNOSIS. 

number of c.c. of the potassium sulpho-cyanide solution representing 

the excess of silver nitrate in 100 c.c of the nitrate, and then de- 
ducting the result from 15. it is simpler to multiply by J directly 
and deduct the result from 15. the number of grammes of sodium 
chloride contained in 1000 c.c. of urine being thus found. This 
figure is then corrected for the total amount of urine. 

Hence the equations, I., x = 15 : II.. 1000 : x : : A : Ch. 

A (15- I 



or the combined formula Ch 



1000 



in which Ch represents the quantity of chloride- contained in the 
total amount of urine, A the amount of urine actually passed, n the 
number of c.c. of the KSCN solution used in the precipitation of 
the excess of chlorides in 80 c.c. of the filtrate. 

(!» — -) 
So in rue above case Ch = 600 — = «.0o. 

1000 

The method described may be employed in the presence of albu- 
min, albumoses. peptones, and sugar: the urine, however, must be 
fresh, so as to insure the absence of nitrous acid. 

Direct Method. If absolute accuracy is not required, the follow- 
ing method may be employed: 

Ten c.c. of urine are diluted with distilled water to 100 c.c. and 
treated with a few drops of a solution of potassium chromate. This 
mixture is titrated with a one-tenth normal solution of silver nitrate 
until the end-reaction — i. -:.. the occurrence of a faint orange tinge. 
which no longer disappears on stirring — is reached. The number 
of c.c. used multiplied by 0.01 will indicate the amount of chlorides 
present in 10 c.c. of urine. 

As uric acid, the xanthin bases, hyposulphites, sulpha -cyanides. 
and pigments are also precipitated by the silver nitrate, the end- 
reaction is delayed; moreover, unless the urine be very pale, its 
recognition may be difficult, and the error thus caused quite con- 
siderable. This is especially true of febrile urines which contain 
only a small amount of chlorides. 

Should iodides or bromides have been taken, these must first be 
removed, as the iodide and bromide of silver, which are insoluble 
in nitric acid, would give too high a value. 

To this end the following method, which is a very accurate one. 






THE URINE. 305 

should be employed, its only disadvantage being the amount of 
time required. 

Estimation of the Chlorides after Incineration (according- to 
Neubauer and Salkowski). The principle of this method is the 
destruction of all organic material and the subsequent estimation of 
the chlorides contained in the mineral ash, by one of the methods 
described. 10 c.c. of urine are evaporated to dryness in a platinum 
crucible at a temperature slightly below 100° C, after the addition 
of a little pure, dried carbonate of sodium and from 3 to 5 
grammes of potassium nitrate. The addition of the carbonate of 
sodium converts any ammonium chloride which may be present 
into sodium chloride; the potassium nitrate merely acts as an 
oxidizing agent. The residue is now carefully heated at a moder- 
ate temperature, allowed to cool, dissolved in distilled water, and 
accurately neutralized with very dilute nitric acid. In this solu- 
tion the chlorides are estimated most conveniently according to the 
second method. 

Should iodides or bromides be present, the aqueous solution just 
referred to is acidified with hydrochloric acid and the iodine and 
bromine thereby liberated extracted with carbon disulphide. As 
complete removal of these bodies is, however, only possible in the 
presence of a nitrite, it is better not to rely upon the presence of 
any that may have been formed during the process of incineration, 
but to add a few drops of a solution of potassium nitrite. After 
extraction the nitrous acid is decomposed by the addition of a little 
urea. The solution is then neutralized with sodium carbonate ; 
should it be alkaline, dilute acetic acid is added until neutral. In 
this solution the chlorides are most conveniently estimated according 
to the second method. 

Albumin and sugar, if present, should be removed before the 
addition of the sodium carbonate and potassium nitrate, if this 
method is employed, so as to obviate losses from sputtering, which 
would otherwise occur. Nitrous acid must also be removed for 
reasons given above. 

The Phosphates. 

The phosphates occurring in the urine are sodium, potassium, 
calcium, and magnesium salts of the tribasic acid H 3 P0 4 , the most 
important of which, as was pointed out in the chapter on Reaction, 
is the diacid sodium phosphate XaH 2 P0 4 , to which the acidity of 

20 



306 CLISICAL DIAGNOSIS 

the urine is due. It is owing to the presence of this salt in the 
urine that the calcium phosphate is held in solution: the fact, at 
least, that calcium and magnesium phosphates are thrown down 
when the urine is neutralized would point to this conclusion. 

The composition of the phosphates is liable to considerable varia- 
tion, depending upon the degree of acidity of the urine. As would 
be expected, diacid sodium phosphate and diacid calcium phosphate 
are present in an acid urine : in an amphoteric urine, in addition 
to these there are found disodium phosphate, monocalcinm phos- 
phate, and monomagnesinm phosphate, while in an alkaline urine 
trisodie phosphate, neutral calcium phosphate, and neutral magne- 
sium phosphate may be present. 

The alkaline phosphates normally exceed the earthy phosphates 
by one-third, and sodiam is combined with far the greater amount 
of phosphoric acid, the potassium salt normally occurring in only 
very small amount-. 

In addition to the mineral phosphates, phosphoric acid is also 
excreted in combination with glycerine as glycerine-phosphoric acid,, 
which need not. however, be considered in a quantitative estimation, 
as it is present only in traces. 

As in the case of the chlorides, the phosphates are derived from 
two sources, by far the greater part being derived from the food, 
while only a small portion is referable to the phosphorus built up 
in the proteid molecule, be this in the form of a muscle-cell, nerve- 
cell, red blood- corpuscle, or bone. But just as the percentage of 
sulphur varies in the different tissues, so also does that of phos- 
phorus vary: nerve-tissue, for example, which is very rich in 
lecithin and nuclein. yields relatively more phosphorus than 
muscle-tissue. 

Xot all the phosphoric acid ingested, however, is excreted in the 
urine, one-third to one-fourth of the total quantity being eliminated 
in the feces. 

The quantity of P 2 5 excreted, which normally varies between 
2.5 and 3 grammes, is thus largely dependent upon the amount 
invested, increasing with an animal and decreasing with a vegetable 
diet. During starvation the excretion of P 2 5 is largely increased, 
in consequence, no doubt, nf an increased destruction of bony tissue, 
which is very rich in the phosphates of the alkaline earths. In ac- 
cordance with this view, calcium and magnesium are excreted in 
increased amount during starvation. The relation between the ex- 



THE URINE. 307 

cretioD of P a O g and N, normally 1 : 7, changes, moreover, in such 
a manner that both the absolute and relative amount of phosphoric 
acid as compared with the nitrogen increases, leading to the conclu- 
sion that in addition to the muscles some other tissue, rich in phos- 
phorus and relatively poor in X, must suffer during the process, 
the only one that suggests itself being bone. 

If at this time food containing phosphorus be again given, a 
retention will take place in the body, so that the general rule given 
iu the chapter on Chlorides, that increased elimination is followed 
by a certain degree of retention, and that a previous retention is 
followed by an increased elimination, seems to hold good for all the 
mineral acids found in the urine (see also the chapter on Sulphates). 
An increased elimination is also caused by the ingestion of large 
quantities of water, which is followed by a certain degree of reten- 
tion. 

Observations made upon the phosphatic excretion during mus- 
cular exercise have not given uniform results, apparently depending 
upon the nature of the food, as a decrease, no effect at all, and an 
increase have been reported by different observers. Mental exer- 
cise appears to cause a diminished excretion of the alkaline phos- 
phates and an increased elimination of the earthy phosphates. The 
latter also takes place during sleep. 

The factors which influence the exact nature of the individual 
phosphatic salts have been considered in the chapter on Reaction, 
in which this has been shown to depend upon the alkalinity of the 
blood, and ultimately upon the quantity of acid set free by the 
tissues or which has been absorbed during the process of digestion; 
increased tissue-destruction, of course, likewise causes an increased 
elimination of phosphates. 

Pathologically the total amount of phosphates eliminated in 
twenty-four hours may either be increased or diminished. 

A diminished elimination is observed in most cases of acute febrile 
disease, such as pneumonia, typhoid fever, typhus fever, recurrens, 
during a paroxysm of intermittent fever, etc., the degree of diminu- 
tion being usually proportionate to the severity of the disease, reach- 
ing its lowest figure as death approaches. Such a state of affairs 
may, at first sight, appear paradoxical, in view of what has been 
said above of the effects of tissue-destruction upon the elimination 
of phosphates. It is necessary, however, to distinguish sharply 
between an increased production and an increased elimination, a 



3ns 1LIWICAL DIAGNOSIS 

retention of the phosphates actually set free from the tissues, analo- 
gous to the retention of chlorides before noted, in all probability 
taking place. It has been supposed that the phosphates set free 
during the process of tissue-destruction are utilized in the building 
up of new leucocytes, an increase in which is actually noted in some 
of the diseases mentioned. 

A diminished excretion of phosphates is, however, not always 
observed, and an increased elimination, on the other hand, may 
occur in certain cases. In fatal cases this condition may even 
persist until the time of death. I: :- very difficult to give a satis- 
factory explanation of this fact at the present time. The phenom- 
enon, in typhoid fever at least, appears to be connected with the 
intensity of the nervous _:;:r nations, and Robin concludes that 
here an increased elimination during the fastigium is an unfavor- 
able omen, while an increase during defervescence warrants a 
favorable prognosis. A similar decrease in the phosphates has 
also been observed in pulmonary phthisis associated with high 
fever. 

Very ii^rr-ting and important is the diminished excretion of 
phosphate ass>:-:at*d with acute an:: : some extent also, with 
chronic nephritis, amyloid degeneration of the kidneys, and the 
anaemias, in which an actual insufficiency on the part of the kidneys 
in the elimination of these salts appears to exist. 

A diminished, or. at least, no increased excretion is seen in certain 
diseases of the bones, such as osteomalacia, although an increase in 
the earthy phosphates has been noted. This may depend upon 
either a retention or an elimination through other channels. The 
earthy phosphates especially are found in greatly diminished amount, 
or may even be absent altogether in certain cases of nephritis. A 
similar condition is observed in acute and chronic rheumatism. 

During attacks of hysteria major, in contradistinction to epilepsy, 
in which an increased elimination takes place, the phosphates are 
diminished, the degree of diminution being generally proportionate 
: the intensity of the attack, increasing again together with the 
other urinary constituents with the subsequent increase in the 
diuresis. The data regarding the phosphatic elimination in 
nervous and mental diseases are, on the whole, very scanty and 
no means uniform. In chronic lead-poisoning a diminution 
to one-third of the normal quantity may occur. Very low figures 
have been noted in Addison's disease, in acute yellow atrophy, in 



THE URINE. 309 

which eveD a total absence may occur, and in certain cases of 
hepatic cirrhosis. 

An increased elimination of phosphates, on the other hand, 
amounting in some eases to 7 or even to 9 grammes in the 
twenty-four hours, has been described under the name of phos- 
phatic diabetes, the patient presenting various symptoms commonly 
seen in diabetes mellitus, sugar, however, being usually absent. 
Whether or not phosphatic diabetes is a disease sui generis is not 
as yet certain. 

In true diabetes mellitus a curious relation has been found to 
exist between the elimination of sugar and of phosphates, the quan- 
tity of the latter rising and falling in an inverse ratio to the amount 
of sugar. In diabetes insipidus a slight increase is at times found. 

Corresponding to the phosphatic retention observed in acute 
febrile diseases an increased elimination is noted during convales- 
cence. In meningitis, especially in cerebro-spinal meningitis, an 
increase occurs in the course of the disease. 

Recently an increase to 7 grammes was noted in a case of pseudo- 
leukemia, in which the number of red corpuscles fell from 2,200,000 
to 800,000 in four days, and in which, to judge from the very care- 
ful observations made, there could be no doubt that the high degree 
of phosphaturia, which was limited to the alkaline phosphates, was 
referable to this source. In a case of leukaemia also an increase 
to 7 grammes was observed on the day preceding death; commonly, 
however, the increase is but slight in this disease. 

While it is apparent that important conclusions cannot be drawn, 
on the whole, from a knowledge of the absolute phosphatic elimina- 
tion, unless it be from a study of the relation existing between the 
excretion of the alkaline and earthy phosphates, a study of the rela- 
tive phosphatic excretion seems to promise more valuable results. 
According to Ziilzer, a certain amount of the phosphates and of the 
nitrogen is referable to the destruction of albuminous material, so 
that the relation between the phosphoric acid and the nitrogen must 
be a constant one. Another portion, however, is derived from leci- 
thin, one of the most important constituents of nerve-tissue, contain- 
ing more phosphorus than the albuminous molecule. Whenever, 
then, the lecithin-containing tissues are more involved in the gen- 
eral metabolism than under normal conditions, this relation will no 
longer be a stable one. 

This relation which exists between the elimination of nitrogen 



310 CLINICAL DIAGNOSIS. 

and phosphoric acid has been termed the Relative Value of phos- 
phoric acid. 

The relative value of phosphoric acid in the urine has been calcu- 
lated as varying from 17 to 20, that of the blood being 3, of muscle- 
tissue 12.1. of brain 44, of bone 426 to 430. This value supposes 
the absolute value to vary between 2 and 3 grammes pro die. It 
is found according to the following equation: 

H : ? : 100 : x. and x = 10 ° ' P A. 

N 

in which X indicates the amount of nitrogen actually observed. 
P 2 3 the amount of phosphoric acid in the same specimen of urine, 
and x the amount of P.,0 3 corresponding to 100 grammes of N. 
By observing this relative value a much better idea may be formed 
of the processes taking place in the body in disease than from a mere 
expression of the absolute phosphatic value. 

In acute febrile diseases the relative as well as the absolute 
diminution of the phosphates has been ascribed, as mentioned 
above, to their retention, they being possibly utilized in the 
building up of white blood-corpuscles. In the course of these 
diseases oscillations in the relative value are frequently observed, 
and an increased relative amount would be explained by assuming 
a transformation of leucocytes rich in phosphorus into red cor- 
puscles, which are relatively poor in phosphorus, resulting in a 
liberation of P 2 3 . During convalescence the relative as well as 
the absolute value again rises. 

In accordance with these considerations a diminished relative 
excretion of phosphoric acid should be expected in all cases asso- 
ciated with a notable elimination of pus-corpuscles through other 
channels, as in pneumonia, for example, or a storing away of the 
same, as in cases of empyema. The facts observed are in accord 
with this view. 

A relative decrease has further been noted in the various forms 
of ameinia, conditions of cerebral excitation, and especially pre- 
ceding an attack of epilepsy. In progressive paralysis following 
svphilis the relative value, at first low, rises greatly after the admin- 
istration of potassium iodide, while the excretion of the earthy phos- 
phates is lessened. In chronic cerebral affections, delirium tremens, 
and acute hydrocephalus a relative decrease has been noted. In 
mania, during the | : :itement, both the alkaline and 

earthy phosphates are found increased, while during the stage of 



THE URINE. 311 

depression, as also in melancholia, the alkaline phosphates are 
found in diminished and the earthy in increased amount. On the 
other hand, an increase in the relative value has been noted in apo- 
plexy (amounting to 34.3 in one case two days after an attack), 
brain-tumors, tabes, arthritis deformans (30), pernicious anaemia 
(23.8-58), etc. 

Of drugs potassium bromide appears to diminish the absolute 
amount of phosphoric acid. Cocaine and quinine cause a decrease, 
and salicylic acid an increase. A relative decrease is produced by 
the cerebral excitants, such as strychnine, small doses of alcohol, 
phosphorus, valerian, cold baths, salt-water baths, etc. An opposite 
effect is produced by the cerebral depressants, such as chloroform, 
morphine, chloral, large doses of alcohol, potassium bromide, min- 
eral and vegetable acids, prolonged cold baths, Turkish baths, low 
temperature. 

As is apparent from the data given, our knowledge concerning 
the excretion of phosphoric acid is as yet in its infancy, and the 
causes producing variations in its amount very obscure. It is 
quite apparent, nevertheless, that a detailed study, especially of 
the relative excretion of phosphoric acid, would, in all probability, 
lead to highly important results, permitting an insight into the 
metabolism of the individual body- tissues, as it were. In this 
connection the observations of Edlefsen, on the relation existing 
between the destruction of leucocytes and the excretion of P 2 5 , 
deserve especial mention. 

Practical data as to diagnosis and treatment can, however, not 
yet be formulated. 

Tests for the Phosphates in the Urine. The test for the detec- 
tion of the phosphates occurring in the urine depends upon the pre- 
cipitation of phosphoric acid by means of ferric chloride as ferric 
phosphate, which is insoluble in cold acetic acid, according to the 

equation : 

2NaH 2 P0 4 + Fe 2 Cl 6 = Fe 2 (P0 4 ) 2 + 2NaCl + 4HC1, 
or 

2Xa. 2 HP0 4 + Fe 2 Cl 6 == Fe 2 (P0 4 ) 2 + 4NaCl + 2HC1. 

The same result may be accomplished by the addition of a solution 
of uranvl nitrate, giving rise to the formation of uranyl phosphate, 
which is also insoluble in acetic acid, according to the equation: 

Xa 2 HP0 4 + 2UO.NO a == 2NaN0 8 -f- iUO) 2 FIP0 4 , 
or 

NaH 8 P0 4 + UO.N0 8 = NaN0 3 +UO.H 2 P0 4 . 



312 CLINICAL DIAGNOSIS. 

Test: A few c.c. of urine are acidified with a few drops of acetic 
acid, and treated with a few drops of a solution of ferric chloride 
(one part of the officinal solution to ten parts of water), when the 
occurrence of a yellowish- white precipitate will indicate the pres- 
ence of phosphates. 

If a solution containing an acid phosphate of the alkalies be 
treated with an alkaline hydrate, the diacid alkaline phosphate is 
transformed into the monacid salt, according to the equation : 
NaH 2 P0 4 + NH 4 OH = NaNH 4 BT0 4 + H 2 0. 

This is further changed into the normal salt, as represented in the 
equation: 

3NaNH 4 HP0 4 + NH 4 OH = Na 3 P0 4 + (NH 4 ) 3 (P0 4 ) 2 + H 2 0. 

As the monacid and neutral salts are both readily soluble, the 
solution remains clear. If at the same time, as in the urine, a 
soluble diacid phosphate of the alkaline earths be present, this is 
likewise transformed into the monacid, and finally into the neutral 
salt; the latter, however, being insoluble, is thrown down: 

I. Ca(H 2 P(V 2 + 4NH 4 OH = Ca(NH 4 ) 2 (P0 4 ' 2 + 4H 2 0. 
II. 3Ca;XH 4 ) 2 (P0 4 > 2 = Ca 3 (P0 4 ) 2 + 2[NH 4 3 P0 4 . 

Test for the earthy phosphates : About 10 c.c. of urine are rendered 
alkaline with ammouia, when the occurrence of a flocculent precipi- 
tate will indicate their presence. 

Test for the alkaline phosphates : After having removed the earthy 
phosphates from 10 c.c. of urine, as just described, the clear filtrate 
is acidified with acetic acid and tested with ferric chloride, or uranyl 
nitrate, as shown above. 

The alkaline phosphates may also be detected by treating the 
ammoniacal filtrate with a few drops of magnesia mixture (1 part 
of crystallized magnesium sulphate, 2 parts of ammonium chloride, 
4 parts of ammonium hydrate, and 8 parts of distilled water), when 
ammonio-magnesium phosphate, which is almost insoluble in ammo- 
nium hydrate, will be thrown down, the reaction taking place be- 
tween the monacid or neutral sodium phosphate and the magnesium 
sulphate, according to the equation: 

Na 2 HP0 4 4-MgS0 4 +NH 4 OH+NH 4 Cl=MgNH 4 P0 4 +NH 4 Cl+Na 2 S0 4 ^H,0. 

Quantitative Estimation of the Total Amount of Phosphates 
Principle : When a solution of disodium phosphate, acidified with 
acetic acid, is treated with a solution of uranyl nitrate, or uranyl 



THE URINE. 313 

acetate, a dirty-looking, white precipitate of uranyl phosphate [a 
thrown down, which is formed according to the equation given 
above. 

It is apparent that the quantity of P 2 5 can be estimated accu- 
rately if the solution of uranyl nitrate or acetate be of known 
strength. 

Solutions required : 

1. A solution of uranium nitrate of such strength that 20 c.c. 
shall correspond to 0.1 gramme of P 2 5 . 

2. A solution containing acetate of sodium and acetic acid. 

3. Tincture of cochineal. 
Preparation of these solutions : 
1 . From the equation : 

2UO.N0 3 + Xa 2 HP0 4 = (UO) 2 HP0 4 + 2NaN0 3 

it is apparent that 2 molecules of uranium nitrate combine with 1 
molecule of disodium phosphate to form uranium phosphate and 
sodium nitrate. The molecular weight of uranium nitrate being 
318 and that of disodium phosphate 142, it is seen that 636 parts by 
weight of the former combiue with 142 parts by weight of the latter. 

As 20 c.c. of the solution of uranium nitrate correspond to 0.1 
gramme of P 2 5 , 1000 c.c. must be equivalent to 5 grammes of P 2 0-. 
In 142 parts by weight of disodium phosphate there would be present 
71 grammes of P 2 O s , equivalent to 636 parts by weight of uranium 
nitrate. The quantity of the latter, then, to be dissolved in 1000 
c.c. of water would be found from the equation: 636 : 71 : : x : 5; 
and x = 44.78. 

44.78 grammes of uranium nitrate are weighed off and dissolved 
in about 900 c.c. of water, the solution being purposely made too 
strong for reasons pointed out in the chapter on Chlorides. In 
order to bring this solution to its proper strength it is necessary to 
titrate with the uranium solution a solution of disodium phosphate 
of such strength that every 50 c.c. shall contain 0.1 gramme of P 2 CX,, 
or 1000 c.c. 5 grammes. The molecular weight of Na 2 HP0 4 - 
12H 2 being 358, this amount of disodium phosphate in grammes 
is equivalent to 179 grammes of P 2 5 ; the quantity of P 2 5 corre- 
sponding to 5 grammes, in terms of Xa 2 HP0 4 -f 12H 2 0, is found 
from the equation : 358 : 179 : : x : 5; and x = 10. Ten grammes 
of pure, dry, and non-deliquescent Xa 2 HP0 4 are dissolved in 1000 
c.c. of distilled water. If non-deliquescent disodium phosphate be 



314 CLINICAL DIAGNOSIS. 

not at hand, about 12 grammes of the salt are dissolved in 1000 c.c. 
of distilled water; of this solution 50 c.c. are evaporated in a 
weighed platinum dish, and the residue gently heated, the disodium 
phosphate being thereby transformed into sodium pyro-phosphate, 
Na 4 P 2 7 , according to the equation: 

2tfa 2 HPO i = Na 4 P 2 7 + H 2 0. 

The molecular weight of Na 4 P 2 7 being 266, this corresponds to 142 
grammes of P 2 5 . 

If the solution were of the correct strength — i. e., containing 0.1 
gramme of P 2 5 in 50 c.c. of water — the residue should weigh 0.1873 
gramme, as is seen from the equation: 142 : 266 : : 0.1 : x; and x = 
0.1873. Supposing, however, the residue to weigh 0.1921 gramme, 
it is manifest that the solution is too strong, and must be diluted, 
the degree of the dilution being determined according to the equa- 
tion : 0.1873 : 1000 : : 0.1921 : x; and x = 1025; i. e., 1000 c.c. of 
the solution made must be diluted to 1025 c.c. to make it of the 
proper strength. 

In the case given 50 c.c. were used; the 950 c.c. are then diluted 
with the amount of water found from the equation : 1000 : 1025 : : 
950 : x; and x = 953.75. Having thus obtained a solution of diso- 
dium phosphate of such strength that every 50 c.c. shall contain 0.1 
gramme of P 2 5 , this solution is titrated with the uranium solution 
which has been made too strong, in order to determine the amount 
of water that must be added to the latter. To this end a Mohr's 
burette is filled with the uranium solution; 50 c.c. of the disodium 
phosphate solution are treated with a few drops of the tincture of 
cochineal and 5 c.c. of the acetic-acid mixture (see below). This 
mixture is heated in a beaker and, as soon as the boiling-point has 
been reached, titrated with the uranium solution until a trace of a 
greenish color is noticed in the precipitate which does not disappear 
on stirring. This point having been accurately determined by means 
of a second titration, the number of c.c. of distilled water with which 
the remaining solution must be diluted is determined according to 

N. d 
the formula : C = — — , in which C represents the number of c.c. 

which must be added, N the number of c.c. remaining after the 
test-titrations, n the number of c.c. consumed in one titration to 
bring about the end- reaction, and d the difference between the num- 
ber of c.c. used in one titration and that theoretically required. 



THE URINE, 315 

The amount of distilled water necessary for dilution is now added 
and the solution again tested, when 20 c.c. will correspond to 0.1 
gramme of P 2 ( ) 5 . 

2. The acetic-acid mixture consists of about 100 grammes of 
acetate of sodium dissolved in distilled water, and 100 c.c. of a 30 
per cent, solution of acetic acid, the whole being diluted to 1000 c.c. 

3. Tincture of cochineal. This may be prepared as follows: A 
few grammes of cochineal granules are digested at ordinary tem- 
peratures with 250 c.c. of a mixture of 3 volumes of water and 1 
volume of 94 per cent, alcohol. The solution is then decanted 
and ready for use. The residue may be utilized iu the preparation 
of a fresh supply of the tiucture. 

Application to the urine: 50 c.c. of clear, filtered urine are treated 
with 5 e.c. of the acetic-acid mixture, the object being to transform 
any monacid sodium phosphate present into diacid sodium phosphate, 
and to neutralize any nitric acid that may be formed during the 
titration, as otherwise the nitric acid would cause a partial solution 
of the precipitated uranyl phosphate. A few drops of the tincture 
of cochineal are added, when the mixture is heated to the boiling- 
point, and titrated as directed above, two titrations being usually 
required. 

The results are then calculated as follows: Supposing 15 c.c. of 
the uranium solution to have been used, the corresponding amount 
of P.O. contained in 50 c.c. of urine is found from the equation: 
20 : 0.1 : : 15 : x; and x = 0.075. The percentage-amount would, 
hence, be 0.075 X 2 = 0.15. Supposing the total amount of urine 
to have been 2000 c.c, the elimination of P 2 5 would correspond 
to 3 grammes. 

The presence of sugar and albumin does not interfere with this 
method. 

Separate Estimation of the Earthy and Alkaline Phosphates. 
If the alkaline and earthy phosphates are to be determined separately, 
the total amount of P 2 0- is estimated in one portion of the urine, 
while the P 2 5 in combination with the alkaline earths is deter- 
mined in another, as follows: 

Two hundred c.c. of filtered urine are made strongly alkaline 
with ammonium hydrate and set aside, covered, for several hours, 
when the earthy phosphates thus precipitated are collected upon a 
filter, washed with dilute ammonia (1 : 3), and then transferred to a 
beaker, with the aid of a little water containing a few drops of acetic 



316 CLINICAL DIAGNOSIS. 

acid, by perforating the filter. They are then dissolved with as 
little acetic acid as possible, diluted to 50 c.c. with distilled water, 
and titrated with the uranium solution as described. The difference 
between the total amount of P 2 5 and the amount thus obtained is 
the quantity of alkaline phosphates present. 

Removal of the Phosphates from the Urine. Whenever it is 
necessary to remove the phosphates from the urine in the course of 
an analysis, as is frequently the case, the urine is rendered alkaline 
by the addition of the hydrate of an alkaline earth and precipitated 
with a soluble calcium or barium salt. The phosphates may also be 
precipitated by means of neutral or basic acetate of lead, in which 
case the excess of lead is removed by means of sulphurated hydrogen 
or dilute sulphuric acid. 

The Sulphates. 

The sulphuric acid found in the urine is derived essentially from 
the albuminous material which is constantly broken down in the 
body, only a very small portion of the inorganic sulphates excreted 
being referable to the mineral constituents of the food. As was 
pointed out in the chapter on Reaction, sulphuric acid is constantly 
produced in the body, and, coming into contact with the so-called 
neutral phosphates present in almost all the tissues, transforms 
these into acid phosphates taking up the alkali thus set free, ac- 
cording to the equation : 

2Na 2 HP0 4 + H 2 S0 4 = 2NaH 2 P0 4 -f Na 2 S0 4 , 

both appearing in the urine. The alkaline carbonates, derived from 
the organic salts ingested by a process of oxidation, are also attacked 
by the sulphuric acid. 

As the amount of food ingested is gradually diminished a point 
is reached when the body most tenaciously holds any alkaline salts 
that may still be present, and a new source for the neutralization 
of the acid is found in the ammonia, which would otherwise have 
been transformed into urea. 

While the greater portion of the sulphuric acid excreted in the 
urine is found in the form of mineral sulphates, about one-tenth of 
the total amount may be shown to be in combination with aromatic 
substances belonging to the oxy-group, most important among these 
being the salts of phenol, indoxyl, and skatoxyl. 

Indoxyl and skatoxyl, as will be shown later on, are derived from 
indol and skatol, which, together with phenol, are formed during 



THE URINE, 317 

the process of intestinal putrefaction, their amount Increasing and 
decreasing with the degree of putrefaction, and hence serving as a 
direct index of its intensity. 

The mineral sulphates have been termed preformed sulphates, in 
contradistinction to the others, which are known as conjugate or 
ethereal sulphates. In the following pages the former will be desig- 
nated by the letter A, the conjugate sulphates by the letter B, and 
the total sulphates as A + B. 

The amount of A + B excreted in the twenty-four hours by a 
normal individual varies between 2 and 3 grammes, the ratio of A 
to B being as 10 : 1. 

From what has been said it is apparent that the elimination of 
sulphates through the urine is largely dependent upon the degree 
of albuminous decomposition taking place in the tissues and fluids 
of the body, and hence to a certain extent upon the quantity of 
proteid material ingested, the mineral sulphates occurring in such 
small amount in the food as scarcely to affect the quantity excreted. 
Secondarily, the degree of intestinal putrefaction plays a role. The 
excretion of A + B is thus increased by a diet rich in animal pro- 
teids; the time after a meal, however, at which such an increase can 
be demonstrated varies greatly, depending essentially upon the time 
necessary for digestion. With a vegetable diet, on the other hand, 
the total sulphates will be found in diminished amount. During 
starvation, A -j- B is, of course, also diminished, this diminution 
affecting A especially, but in some cases B may be considerably 
increased. 

Our present knowledge regarding the excretion of sulphates is 
very meagre, as may be seen from the following data : An increase 
in the elimination of the total sulphates is observed, as woidd be 
anticipated, in all cases in which an increased tissue-destruction is 
taking place, as in the acute febrile diseases. It must be remem- 
bered, however, that here the quantity excreted is not always greater 
than during convalescence, the diet remaining the same. Here, as 
elsewhere, in urinary studies, it is always necessary to distinguish 
between a relative increase and an absolute decrease. In pneumonia 
and acute myelitis the highest figures have been observed, the in- 
creased elimination during the febrile period being especially marked : 

Fever diet. Full diet. 





Fever. 


No fever. 


No fever. 


Pneumonia 


. . 3.51 g. 


1.47 g. 


2.25 g. 


Acute myelitic . 


. 2.G2 g. 


1.52 g. 


2.33 g. 



318 CLINICAL DIAGNOSIS. 

Daring convalescence the excretion of the sulphates is diminished, 
a retention analogous to that of the chlorides and phosphates taking 
place. In contradistinction to the latter salts, it is in all probability 
not the mineral matter proper that is demanded by the body, but 
the sulphur-containing albuminous material. 

A considerable elimination of A -f B has also been observed in 
leukaemia, in which an average of 2.46 grammes is excreted, 
as compared with 1.51 grammes by a healthy individual receiving 
the same amount and kind of food. In one case of acute leukaemia 
5.8 grammes were eliminated on the day preceding death. In 
diabetes mellitus, diabetes insipidus, oesophageal carcinoma, pro- 
gressive muscular atrophy, pseudo-hypertrophic paralysis, and 
eczema an increased elimination has likewise been observed, while 
in chronic renal diseases a diminished excretion is the rule. 

A study of the elimination of the conjugate sulphates and of the 
relation existing between A and B in disease is still more impor- 
tant than that of the total sulphates; but in both cases the data 
available at the present time are very scanty, and further observa- 
tions are urgently needed. 

The conjugate sulphates, as would be expected, are increased in 
all cases of increased intestinal putrefaction. In coprostasis the 
result of carcinoma the ratio of the preformed to the conjugate 
sulphates, normally 10, may diminish enormously. In one case, 
reported by Kast and Baas, it fell to 2, to rise again to 7 to 8, and 
finally to 9.5 to 15 after an artificial anus had been established. 
The author has observed a drop to 1.5 in a case of volvulus of ten 
days' standing. Biernacki found an increase in the elimination of 
conjugate sulphates amounting to from 0.15 to 0.5 gramme pro die 
in cases of chronic parenchymatous nephritis, going hand in hand 
apparently with a decrease in the secretion of hydrochloric acid by 
the stomach, the normal amount, according to his observations, 
being from 0.1973 to 0.2227 gramme. In one case B fell from 
0.4382 to 0.1505 during the administration of hydrochloric acid, 
to increase again to 0.4127 upon its discontinuance. 

In accord with these observations are those of Wasbutzki and 
Kast, the former finding an increased elimination of B in cases of 
intense bacterial fermentation taking place in the stomach, hydro- 
chloric acid being either totally absent or present in greatly dimin- 
ished amount, while a diminished elimination was observed in cases 
of intense torular fermentation, hyperchlorhydria existing at the 



THE URINE. 319 

same time. l\\ the absence of hydrochloric acid, a normal or even 
a slightly diminished amount was observed iii cases of intense acid 
fermentation, lactic and butyric acids being present in large quan- 
tities. 

By neutralizing the gastric juice with large closes of sodium bicar- 
bonate Kast was able to bring about a marked increase in the elimi- 
nation of B, the ratio A: B having fallen from 10.3-16.1 to 2.9-6.1. 

Personal observations have led the author to the same conclusion, 
-i) that the following rules may be formulated : 

1. A diminution in the secretion of hydrochloric acid is accom- 
panied by an increased degree of intestiual putrefaction. 

2. An increase in the secretion of hydrochloric acid is usually 
ac :ompanied by a decrease in the degree of intestinal putrefaction. 

•'). The degree of intestinal putrefaction may be measured directly 
by the elimination of the conjugate sulphates. 

(See also the chapter on the Aromatic Bodies.) 

In obstructive jaundice the excretion of B was likewise found to 
be increased, returning to the normal as soon as the permeability 
of the biliary passages had again become established, while the total 
sulphates were found in diminished amount in cases of non-obstruc- 
tive jaundice. 

In cases of diarrhoea A -f- B, as well as B, is diminished, while 
A : B is increased. 

Of drugs, large doses of morphine, potassium bromide, sodium 
salicylate, and antifebrin appear to cause an increased elimination 
of the total sulphates, while alcohol slightly diminishes the excre- 
tion. 

Most important are the observations which have established a 
diminished excretion of the conjugate sulphates following the inges- 
tion of the terpenes and camphor, Karlsbad and Marienbad water, 
which latter two, however, at first cause an increase. Kefir, in 
doses of from 1 to 1.5 liters pro die, has proved a most excellent 
remedy with which to check intestinal putrefaction. Injections of 
tannic acid and of a saturated solution of boric acid appear to pro- 
duce but little effect, unless the dose be so large as to cause symp- 
toms of poisoning. 

The points of practical interest in connection with the elimina- 
tion of the sulphates may be summarized as follows, and are con- 
centrated in the elimination of the conjugate sulphates: 

1. An increase in the conjugate sulphates in a general way points 



320 CLINICAL DIAGNOSIS. 

to increased intestinal putrefaction, the direct cause for which must, 
according to our present knowledge, be sought in a total anachlor- 
hydria, or at least a hypochlorhydria of the gastric juice, associated 
with intense bacterial fermentation, provided that lactic acid and 
butyric acid are not present in large amounts; an obstruction to the 
flow of bile and intestinal obstruction may, however, produce the 
same result. 

2. A diminution in the quantity of conjugate sulphates, on the 
other hand, may be referable to hyperchlorhydria associated with 
torular fermentation, ulcer of the stomach forming an exception, in 
which, notwithstanding the fact that conjugate sulphates are fre- 
quently eliminated in increased amount, hyperchlorhydria usually 
exists. 

3. In cases of diarrhoea the absolute as well as the relative quan- 
tity of A — B and B is diminished while A : B becomes greater. 

Tests for the Sulphates in the Urine. The detection of the 
preformed and the combined sulphates in the urine depends upon 
the fact that the sulphates of the alkalies are precipitated by barium 
chloride as insoluble barium sulphate, according to the equation: 

K 2 SO, - BaCl 2 = BaSO, -f 2KC1. 

In the urine the addition of barium chloride at the same time 
causes a precipitation of the phosphates, which must be kept in 
solution by the addition of an acid, acetic acid being employed for 
this purpose whenever the presence of the preformed sulphates is 
to be demonstrated; hydrochloric acid is inadmissible, as it would 
cause the decomposition of the conjugate sulphates and set free the 
H 2 SO thus held. 

To test for the preformed sulphates a few c.c. of urine, strongly 
acidified with acetic acid, are treated with a few drops of a solution 
of BaCl 2 , when in their presence a cloud or a white precipitate, 
referable to the formation of BaS0 4 , will form. 

To test for the conjugate sulphates, 25 c.c. of urine are treated 
with about the same volume of an alkaline barium chloride mixture 
(2 volumes of a solution of barium hydrate and 1 volume of a solu- 
tion of barium chloride, both saturated at ordinary temperatures) 
and filtered after a few minutes, the preformed sulphates as well as 
the phosphates being thus removed. The filtrate is then strongly 
acidified with hvdrochloric acid and boiled, when the occurrence of 
a precipitate will be referable to conjugate sulphates. 



THE URINE. 



321 



Quantitative Estimation of the Sulphates. The principle 
of the method employed is the same as that just described, the 
preformed sulphates coutaiued in the urine forming an insoluble 
precipitate of BaS0 4 when treated directly with BaCl 2 , while the 
combined >ulphates do so only after having been decomposed by 
the addition of strong hydrochloric acid and the application of 
heat. In order to estimate the amount of preformed and con- 
jugate sulphates in the urine it is best to determine the total 
sulphate- in one portion, and the combined sulphates in another, 
the difference between the two giving the preformed sulphates. 



Fig. 



Fig. 78. 






A Gooch filter. 

Quantitative Estimation of the Total 
Sulphates. One hundred c.c. of clear, filtered 
urine are treated with 8 c.c. of hydrochloric acid 
(specific gravity 1.12) and heated to the boiling- 
point, when 20 c.c. of a saturated solution of BaCl 2 
are added. The mixture is kept on the water-bath 
until the BaS0 4 has thoroughly settled down and 
the supernatant fluid appears clear; this usually 
requires about half an hour. The precipitate is 
now filtered off, a Schleich and Schiill filter, or, 
still better, a Gooch filter (Fig. 77), provided 
with a close-fitting plug of asbestos, being em- 
ployed, the whole having been previously dried 
and weighed. Care should be taken never to 
allow the filter to become dry, and small amounts 
of hot water must be added to the last c.c. remaining, the final trace- 
being placed upon the filter with the aid of a rubber-tipped glass 
rod. The precipitate is washed with boiling water until a specimen 

21 



A suction-funnel. 



822 CLINICAL DIAGNOSIS. 

::' the washings is no longer rendered cloudy, even on standing for 
a few minutes, on the addition of a drop of dilute sulphuric acid. 
Gum-like substances, as well as pigments, are removed by washing 
with hot alcohol (70 per cent.), and then filling the filter two or 
three times with ether. A suction-apparatus is necessary, and in 
the absence of a special pump a simple glass tube bent upon itself 
may be employed (Fig. 78). 

If a paper filter has been used, it is placed in a weighed platinum 
or porcelain crucible and ignited. The ash is then heated, at first 
moderately, and almost completely covered with the lid. It is then 
heated, only half covered, from five to seven minutes, until the con- 
tents of the crucible are white. The crucible when cooled is placed 
in a desiccator and weighed, the difference between the first and 
the second weight giving the weight of the BaS0 4 obtained from 
100 c.c. of urine. 

A reduction of some of the BaSO^ usually takes place during the 
process of combustion, owing to the presence of organic matter, so 
that the weight of the BaS0 4 obtained is actually too low. This 
error may be ; are ted in the following manner: The BaS0 4 is 

shed into a small beaker with a small amount of water, colored 
red by a few drops of an alcoholic solution of phenolphthalein, and 
titrated with a one-tenth normal solution of sulphuric acid until 
the red color has disappeared. Every c.c. of the one-tenth normal 
-:•*•_;:; yi c:rr-~::- ::::!- :■:■ 0.004 ^ru^i^c of B;-..^<_>__. ?o :hu: :0r :. ::u^ 
amount of BaS0 4 contained in 100 c.c. of urine is ascertained by add- 
ing the figure thus found to that obtained by weighing (see below). 

Quantitative Estimation of the Conjugate Sulphates. 
One hundred c.c. of clear, filtered urine are mixed with 100 c.c. of 
an alkaline solution of BaCL (see above), the mixture being thor- 
oughly stirred. After a few minutes this is filtered through a dry 
filter into a dry graduate up to the 100 c.c. mark. This portion, 
corresponding to 50 c.c. of urine, is now strongly acidified with 
dilute hydrochloric acid and brought to the boiling-point. It is 
kept upon the boiling water-bath until the BaS0 4 formed has settled 
and the supernatant fluid is clear. The precipitate is filtered off, 
washed, dried, and weighed, as described above. The BaS0 4 thus 
obtained multiplied by 2 and deducted from the amount found 
according to the first method indicates the amount referable to the 
preformed sulphates. The molecular weight of BaS0 4 being 232.82, 
that of BO a 79. B6 3 f H_S<0 :<7. -2, and of S 32, the figure express- 



THE URINE. 323 

ing the amount of H_,S() 4 , S() 3 , or S, corresponding to 1 gramme of 
BaS0 4 , is found according to the following equations ■ 

232.82 : 79.86 : : 1 : x, and x = 0.34301. ,\ 1 gramme of BaSO, 
= 0.34301 gramme of SO s . 

232.82 : 97.82 : : 1 : x, and x = 0.42015. .\ 1 gramme of BaSO, 
= 0.42015 gramme of H 2 SO r 

232. 82 : :V2 : : 1 : x, and x = 0. 13744. . \ 1 gramme of BaS0 4 = 
0.13744 gramme of S. 

To calculate results it is only necessary to multipy the weight of 
BaS() 4 found by 0.34301, 0.42015, or 0.13744 in order to ascertain 
the amount of sulphuric acid contained in 50 c.c. of urine in terms 
of SOj, B^S0 4 , or S, respectively. 

Urea. 

Urea is by far the most important nitrogenous constituent of the 
urine, representing under normal conditions 85 to 86 per cent, of 
the total amount of nitrogen eliminated by the kidneys. Chemic- 
ally it may be regarded as carbamide — i. e., as the amide of carbonic 
acid — and represented by the formula: 

NH 2 

CO< , 
X NH 2 

being thus a comparatively simple substance, and the question natu- 
rally suggests itself, In what relation does urea stand to the highly 
complex albuminous molecule from which it is derived ? Numerous 
hypotheses have been offered to explain this most difficult problem, 
and, although we are in possession of a number of very suggestive 
data, an ultimate answer to the question cannot be given at the 
present time. 

When albumin is treated with strong acids or alkalies, leucin, 
tyrosin, and asparaginic acid are formed, bodies which belong to the 
group of amido-acids, being represented by the formulae: 

C 5 H 10 (NH 2 ) .OH /COOH 

I C 6 II 4 ( C 2 H 3 (XH. 2 )( 

COOH x C. 2 H 3 (NH 2 )COOH N COOII 

Leucin. Tyrosin. Asparaginic acid. 

These bodies were regarded by Schultzen and Nencki as inter- 
mediary products in the formation of urea. As a matter of fact, 
it wae shown that leucin, asparaginic acid, and glycocoll, 

NH, 
X COOH 



324 CLINICAL DIAGNOSIS. 

which latter can be obtained under similar conditions from connec- 
tive tissue, osseous and gelatinous tissue, are transformed, to a large 
extent at least, into urea within the body. An analogous formation 
of urea was hence supposed to occur, the transformation of aruido- 
acids into uric acid occurring in birds being regarded as supporting 
this view, uric acid in birds corresponding to urea in mammals. 
The manner of the transformation of amido-acids into urea in the 
body is unknown. It is conceivable that cyanic acid (COXH), 
for example, may be produced as an intermediary product, the for- 
mation of urea resulting from an interaction between 2 molecules of 
COXH in statu nascendi, according to the equation : 

NH 2 

CO^H - CONH - H 2 = CC< + C0 2 . 

X XH 2 

A transformation of the amido-acids into the ammonium salts of the 
fatty acids standing next in order in the downward scale may also 
be imagined. This change being produced by a process of oxidation, 
the salts of the fatty acids would then be transformed into ammo- 
nium carbonate and this again into urea. 

In the case of glycocoll such a process would be represented by the 
following equations: 

I. CH 2 .^H,.COOH -f 20 = HCO.-XH, - C0 2 

Amido-acetic acid. Ammon. formate. 

II. 2H.C0 2 .XH 4 - 20 = (XH 4 ) 2 C0 3 — H 2 -\- C0 2 
Ammon. formate. Ammonium carbonate. 

NH 2 
III. (yH 4 ) 2 C0 3 =COC - 2H,0. 

X XH 2 

The possible formation of urea from ammonium carbonate in the 
body has been demonstrated by v. Schroeder and Salomon, who 
observed a fair production of urea when blood containing ammo- 
nium carbonate or ammonium formate was allowed to flow through 
isolated livers of dogs. 

Other hypotheses have been offered to explain the mode of for- 
mation of urea, such as its production from ammonium carbonate, 
formed directly from albuminous material without the intermediate 
occurrence of amido-acids. 

According to Drechsel, the amido-acids are transformed into car- 
bamic acid, 2 molecules of the latter uniting to form urea, carbonic 
acid, and water: 



THE URINE. 325 

Ml, MI. ,NH a 

co + co< " = co; -hCOo + H a o. 

X 0H x OII X NII, 

On the other hand, it is possible that urea is not always formed 
in the same manner, and the possibility of its formation from kreatin 
and xantliin bases cannot be altogether excluded. It is also con- 
ceivable that urea may under certain conditions be produced in a 
different manner by different organs. 

Numerous experiments have been made in order to ascertain defi- 
nitely in what organ or organs urea is formed during health, and 
special attention has been directed to the kidneys, the muscular 
tissue, and the liver. 

Opposed to the assumption that urea is formed in the kidneys are 
the facts that after extirpation of these organs an accumulation of 
urea is observed in the blood and tissues of the body, and that 
experiments analogous to those made with still living livers fur- 
nished a negative result. 

The same result has been reached as far as the muscular tissue of 
the body is concerned, although the curious fact that more urea is 
found in these organs than in the blood of nephrectomized animals, 
iu the typhoid stage of cholera Asiatica, etc., has so far not been 
explained. Under normal conditions, however, urea has not been 
demonstrated iu the muscles. 

There remain then for consideration the large glandular organs 
of the body, especially the liver and spleen, in which urea is always 
demonstrable. In the former organ the transformation of ammo- 
nium carbonate and the ammonium salts of the fatty acids has been 
conclusively established. The facts that possible antecedents of 
urea, such as leucin, have been observed in the absence of urea in 
the urine, in cases of acute yellow atrophy, and that an increase in 
the eliminaton of ammonia goes hand-in-hand with a diminished 
excretion of urea in certain diseases of the liver, also speak strongly 
in favor of the hepatic origin, to a large extent at least, of urea. 

Before going on to a consideration of the quantitative excretion 
of urea in health and disease it will be well to form an idea of its 
ultimate sources. To this end the theory of Pettenkofer should be 
recalled, according to which albuminous material exists in the body 
in two different forms — l. e., as organized albumin — which is built 
up in the form of tissues of the body, and as unorganized albumin, 
or circulating albumin, which must be regarded, in a manner, as a 



326 CLINICAL DIAGNOSIS. 

reserve, to be used in tissue-repair, to be broken down if not used, 
and to be replaced by the proteids ingested with the next meal. It 
may, hence, be said that, as in the case of the mineral constituents 
of the urine, the urea found in the urine is referable on the one hand 
to the proteids of the food, and on the other to the proteids of the 
body-tissues. It is clear then that the elimination of urea will con- 
tinue during starvation. 

It has been stated that 8-4 to 86 .6 per cent, of all the nitrogen 
eliminated in the urine is found in the form of urea, the remaiuing 
13.4 per cent, being excreted as uric acid, hippuric acid, kreatinin, 
xanthin bases, etc. It might, hence, be supposed that au accurate 
idea of the degree of tissue-destruction could be formed from a 
quantitative estimation of urea. This, however, is not the case, 
especially in pathologic conditions, as the quantitative relation 
existing between the excretion of urea and the remaining nitro- 
genous constituents is subject to wide variations. In acute yellow 
atrophy, for example, as pointed out above, urea may disappear 
entirely from the urine, the nitrogen being eliminated in the form 
of other compounds. Whenever it becomes desirable then to gain 
an accurate insight into the degree of proteid-destruction or proteid- 
assimilation — in other words, into the nitrogenous metabolism — 
taking place in the body, it is necessary to resort to a quantitative 
determination of the total amount of nitrogen excreted by the kid- 
neys, the quantity found being conveniently expressed in terms of 
urea. At the same time it is customary to express the amount of 
proteid tissue destroyed as muscle-tissue, this serving as a fair type 
of body-tissue in general. 

As 100 grammes of lean muscle-tissue contain about 3.4 grammes 
of nitrogen, corresponding to 7.286 grammes of urea, 1 gramme of 
the latter is equivalent to 13.72 grammes of muscle-tissue. It is, 
hence, only necessary to multiply the quantity of urea eliminated in 
the twenty-four hours, corresponding to the total amount of nitrogen 
found, by 13. 72, in order to form an idea of the extent of albuminous 
destruction taking place in the body. If accurate results are to be 
obtained, it also becomes necessary to determine the amount of nitro- 
gen eliminated in the feces, a knowledge of the quantity in the food 
ingested being, of course, presupposed. 

With all these data given the nitrogenous metabolism of the body 
can be accurately controlled. 

Example : A patient eliminated 50 grammes of urea in twenty- 



THE URINE. 327 

four hours; these 50 grammes correspond to 50 X 13.72 — i. c, 686 
grammes of lean muscle-tissue; he ingested, on the other hand, an 
amount of nitrogenous material corresponding to only 10 grammes 
of urea, equivalent to 10 X 13.72 — /. e., 137.2 grammes of muscle- 
tissue. The difference between the amount ingested and that ex- 
creted in this case — i. e., 548.8 grammes — must be referable to the 
destruction of organized albumin. 

The valuable results of such a study in different cases, and the 
in>ight that can thus be obtained into the metabolic processes taking 
place in the body, are apparent, but such studies are, unfortunately, 
greatly neglected. 

When the amount of nitrogen eliminated is equivalent to that 
ingested, nitrogenous equilibrium is said to exist. A healthy person 
may be said to be approximately in this condition. 

It has been pointed out that during starvation urea is still elimi- 
nated from the body, although in diminished amount. The question 
now arises, What happens if at this time an amount of nitrogenous 
food is given which corresponds exactly in amount to that elimi- 
nated ? Under such conditions an increased elimination of nitrogen 
takes place, all of the nitrogen ingested, in addition to that resulting 
from a breaking down of tissue, being excreted. The amount of 
nitrogen referable to the latter source, however, is somewhat less 
than that eliminated in the total absence of food. Unless starvation 
has been pushed too far, the body accommodates itself to the amount 
of food thus given and nitrogenous equilibrium is restored. If more 
food be allowed, an increased elimination results, again leading to 
a condition of nitrogenous equilibrium, different levels, so to speak, 
being possible. This is well illustrated by comparing the condition 
of the poorly nourished North German laboring population with 
that of the well-fed merchants, the excretion of urea in the former 
amounting only to 17.5 to 33.5 grammes of urea, and in the latter 
to 30 or even 40 grammes. 

It is apparent, then, that the elimination of urea, and of nitrogen 
in general, is subject to great variations, depending upon the amount 
ingested and that resulting from tissue-destruction, which in turn is 
largely influenced by the body-weight. A statement in figures 
expressing the daily elimination of urea and of nitrogen would, 
hence, be of very little value, especially in pathologic conditions, 
in which the amount of nitrogen ingested is frequently very small. 
The elimination of nitrogen should hence always be compared with 



328 CLINICAL DIAGNOSIS. 

the amount ingested, for which purpose the tables of Konig will 
be found most convenient. At the same time it must be remem- 
bered that not all the nitrogen taken into the body as food under- 
goes resorption, and that a variable amount, which in disease may 
be considerable, is eliminated with the feces, so that in accurate work 
this nitrogen also must be taken into account. In order to obviate 
the tedious estimation of nitrogen in the feces it has been proposed 
to determine the standard amount of urea which should appear in 
the urine of a healthy person with different forms of diet. Such 
experiments, of course, presuppose the control-person to be in a 
condition of nitrogenous equilibrium, which, from what has been 
said above, is readily accomplished, the human body adapting itself 
with ease to different forms of diet. In private practice, however, 
such a procedure would be difficult, and here approximate results 
can be obtained by a parallel estimation of the chlorides. In health 
the elimination of the chlorides may be placed at about one-half of 
the urea. Whenever the nitrogen resulting from tissue-destruction 
is in excess of that referable to the proteids ingested this relation 
between the excretion of chlorides and urea will be disturbed, the 
tissues of the body containing but very little sodium chloride. 
Whenever the amount of urea is in excess of the normal amount 
of chlorides, as indicated above, an increased tissue-destruction may 
be inferred, and vice versa. If, on the other hand, the chlorides are 
present in diminshed amount, the conclusion may be drawn that a 
retention of albumins is taking place in the body, a condition which 
is frequently observed during the convalescence from acute febrile 
diseases. 

An increase in the amount of urea, and, as a matter of fact, of all 
the nitrogenous constituents, is observed especially in the acute 
febrile diseases, notwithstanding the diminished ingestion of nitro- 
genous material, and is due to the greatly increased tissue-destruc- 
tion. An excretion of 50 grammes or more of urea is here frequently 
observed. Formerly it was thought that the fever itself was respon- 
sible for this increased elimination of urea; but this view became 
untenable when it was shown that the excretion of urea in the be- 
ginning of a febrile attack is not at all proportionate to the height of 
the temperature, reaching its highest point only when the fever has 
been continuous for several days. Still larger amounts, moreover, 
may be eliminated when the fever is abating. Similar observations 
have since been repeatedly made. An increased elimination of 



THE URINE. 329 

nitrogen may be noted in almost every case of ague preceding the 

onset of the fever. The latter, therefore, cannot be the only factor 
which causes the increased excretion of urea, and it has been sug- 
gested that the cells of the body have lost the power of taking up 
nitrogen. The question, however, whether this is dependent upon 
the increase in temperature or the action of certain toxic substances 
circulating in the blood, or both, must still be regarded as unan- 
swered. 

The large increase in the elimination of nitrogen in febrile dis- 
eases is especially striking in those forms which end by crisis. 
This is notably the case in pneumonia, in which it may persist for 
two or three days after the occurrence of the crisis. This assump- 
tion of an underlying insufficiency on the part of the cells furnishes 
a very satisfactory explanation for the continued increased elimina- 
tion of urea. An increase beyond the amount eliminated during 
the febrile stage is possibly owing to a certain degree of retention 
analogous to that occurring in the case of the mineral constituents 
of the urine. 

The only exception to the rule that the excretion of urea is in- 
creased in acute febrile diseases is, apparently, acute yellow atrophy, 
in which the excretion of urea is not only greatly diminished, but 
may altogether cease, its place being taken by other nitrogenous 
bodies, and notably leucin and tyrosin. 

Among afebrile diseases in which an increased elimination of urea 
has been noted must be mentioned the ordinary forms of diabetes 
mellitus, in which the highest figures have been obtained, viz., 150 
grammes or more pro die. The observation is, in all probability, 
largely explained by the ingestion of excessive amounts of food by 
such patients, but carefully conducted experiments seem to show 
that a not inconsiderable portion of the urea is directly due to in- 
creased tissue-destruction. The interesting cases described by 
Hirschfeld, which will be considered later on, form an exception 
to this rule. 

An increase is also observed in dyspnceic conditions, and particu- 
larly in pneumonia, being most marked on the day following the 
greatest difficulty in breathing. These observations, however, are 
not free from objections, as an increase has also been noted in con- 
ditions of apnoea. 

A moderate increase has been found in cases of pernicious anaemia, 
in severe cases of leukaemia, scurvy, minor chorea, and paralysis 



330 CLISICAL LIAGXOSIS. 

agitans. Observations made in cases of hystero-epilepsy have 

given rise to conflicting results, It is claimed, on the one hand. 
that the excretion of urea is diminished following the convulsive 
seizures of a hystero-epileptie nature, in contradistinction to an 
increased elimination following true epileptic attacks. 

In cases of functional albuminuria associated with an increased 
elimination of uric acid or oxalic acid, or of both, as well as in 
numerous cases of gastro-intestinal disease, the author has observed 
an increased elimination of urea, and believes that in the treatment 
of these diseases a systematic study of the excretion of nitrogen is 
of fundamental importance. 

Of drugs, an increased elimination is produced by coffee, eaffein. 
morphine, codeia. ammonium chloride, sodium and potassium chlo- 
ride, carbonate of lithia. the ingestion of large amounts of water, 
etc. The data concerning the action of quinine, salicylic acid, cold 
baths, etc., are very conflicting. A large increase has been observed 
in cases of phosphorus-poisoning. 

Electricity also appears to exert a marked influence upon the 
excretion of urea, producing an increased elimination. 

The diminish lotion nf area observed in certain disease- of 

the liver, notably in acute yellow atrophy, carcinoma, cirrhosis. 
and even in WeyPs disease, is of especial interest, being in perfect 
accord with the theory that the liver is the main seat of the pro- 
duction of urea. 

As has been stated, urea may altogether disappear from the urine 
in acute yellow atrophy and also inWeyPs disease, notwithstanding 
the frequently not inconsiderable degree of fever. In cirrhosis, 
hyperaemia of the portal system has been thought to cause the dimi- 
nution, which may be further increased in some cases by the occur- 
rence of ascites. In short, the factors which may be regarded as 
causative in the production of a diminished elimination of urea in 
hepatic diseases maybe summarized under the following headings: 

1. Destruction of the hepatic parenchyma. 

2. A diminished velocity of the flow of blood through the liver. 

3. Insufficient excretion of bile, and coincident digestive disturb- 
ances. 

Whenever there is disease affecting that portion of the renal paren- 
chyma which is especially concerned in the elimination of urea, a 
diminished amount will, of course, be met with in the urine, and 
carefullv conducted observations upon the excretion of the various 



THE URINE. 331 

urinary constituents would undoubtedly be of considerable value 
from a diagnostic as well as a therapeutic stand-point. As the 
glomeruli of the kidneys are mainly concerned in the elimination 
of water and salts from the blood, and as the striated epithelium of 
the convoluted tubules appears to provide for the excretion of urea, 
the elimination of a fair amount of the latter with a diminished 
elimination of salts, the phosphates being here of especial interest, 
•a- they are derived to a large extent from albuminous material, 
would point more particularly to glomerular disease. On the other 
hand, a fair excretion of phosphates and a diminished excretion of 
urea would be indicative of tubular disease. Whenever the glom- 
eruli and tubuli contorti are equally diseased an insufficient elimi- 
nation of both phosphates and urea will be observed. 

AVhile, as a rule, the excretion of urea is greatly increased in 
diabetes mellitus, certain cases which have been elaborately de- 
scribed by Hirschfeld must be excepted. His researches have 
established beyond a doubt that the resorption of nitrogenous 
material from the intestines may be very much below normal, and 
with it the elimination of urea. Upon these grounds he has advo- 
cated the recognition of a distinct form of diabetes, which is char- 
acterized by a comparatively rapid course, the occurrence of colicky 
abdominal pains before or at the onset of the diabetic symptoms 
proper, the existence of pancreatic lesions in a certain proportion of 
cases, a more moderate degree of polyuria, etc. 

In mental diseases a diminished excretion of urea has been 
observed in melancholia and iu the more advanced stages of gen- 
eral paresis, while an increase is associated with the increased 
digestion of food during the first stage of profound dementia. 

Following epileptic, cataleptic, and hysterical seizures, as well as 
in pseudo-hypertrophic paralysis, a decrease has been noted by some 
observers. 

The diminished excretion found in Addison's disease has also 
been regarded as being of nervous origin. 

All forms of chronic, non-progressive anaemia are associated with 
a decrease, as are also osteomalacia, impetigo, lepra, chronic rheu- 
matism, etc. In chronic lead-poisoning the elimination of urea 
may be greatly diminished. 

Of the influence of drugs in bringing about a diminished excre- 
tion of urea but little is known. 

In conclusion, the relation existing between phosphatic excretion 



332 CLINICAL DIAGNOSIS. 

and that of nitrogen should be especially noted, and the reader is 
referred to that chapter. 

Properties of Urea. Urea crystallizes in two forms, viz., in 
long, fine white needles, if rapidly formed, or in long, colorless, 
quadratic rhombic prisms when allowed to crystallize gradually 
from its solutions. 

At 100° C. it begins to show signs of decomposition, at 130° to 
132° C. it melts, and when heated still further it is decomposed 
into cyanic acid and ammonia, of which the former is immediately 
transformed into its polymeric compound, cyanuric acid, the reac- 
tion which takes place being represented by the equations: 

7SJTT 

I. COC 2 = CONH + NH 3 . 

X NH 2 

II. 3CONH = C 3 3 N 3 H 3 . 

Biuret is formed as an intermediary product during this decom- 
position, 2 molecules of urea yielding 1 molecule of ammonia and 
1 molecule of biuret, as represented in the equation: 

,NH 2 .NH 2 

co< co; 

co( coc 

X NH 2 X NH 2 

As this substance, which may be obtained by dissolving the resi- 
due remaining after all the ammonia has been driven off by careful 
heating, yields a beautiful reddish- violet color when a drop or two 
of a very dilute solution of sulphate of copper is added to its solu- 
tion alkalinized with sodium hydrate, this reaction may be employed 
as a test for the detection of urea (Biuret Test). 

Urea is readily soluble in water, fairly so in alcohol, and insol- 
uble in anhydrous ether and benzol. The aqueous solution of urea 
is neutral in reaction, but combines with acids, bases, and salts to 
form molecular compounds. 

Of special interest are the compounds of urea with nitric acid, 
oxalic acid, and mercuric nitrate. Urea nitrate, CON 2 H 4 .HN0 3r 
crystallizes in two different forms: in thin rhombic or six-sided 
colorless plates, which are frequently observed arranged like shingles 
one on top of the other when rapidly formed (Fig. 79), while larger 
and thicker rhombic columns or plates are obtained if the process 
of crystallization is allowed to proceed more slowly. Urea nitrate 



THE CHI Si:. 



333 



i> readily soluble in distilled water, while in alcohol and water 
containing nitric acid it dissolves with difficulty. Upon heating it 
evaporates without Leaving a residue. Urea oxalate, ( !ON 2 H 4 C 2 H 2 < ),, 



Fig. 79. 




Nitrate of urea crystals. (Krukenberg, after Kuhne.) 

crystallizes in rhombic or six-sided prisms or plates (Fig. 80), which 
are less soluble in water than the nitrate; in alcohol and water 
containing oxalic acid it is only imperfectly soluble. With mer- 
curic nitrate urea forms three different compounds, according to 



Fig. 80. 




Oxalate of urea crystals. (Krukenberg, after KChne.j 

the concentration of the two solutions, viz., (CON 2 H 4 )Hg 2 (X0 3 ) 4 , 
(COX 2 H 4 ).Hg 3 (X0 3 ) 6 , and (CON 2 H 4 ) 2 .Hg(N0 3 ) 2 + 3HgO. The 
latter compound is of special importance, as Liebig's quantitative 
estimation of urea is based upon its formation. It results when a 



334 CLIXICAL DIAGNOSIS. 

2 per cent, solution of urea is treated with a dilute solution of mer- 
curic nitrate, the reaction taking place according to the equation- 

2C0X. 2 H i -4Hg(NO 3 , ) 2 -3H 2 0=[2(C0X 2 H^ 2 Hg^X0 3 ) 2 ^-3HgO]^6H^0 3 . 

Very important is the behavior of urea when treated with a solu- 
tion of sodium hypochlorite or hypobrornite, the most usual method 
of estimating urea being based upon this reaction, which may be 
represented by the equation: 

COXoH, -f- 3XaOBr = 3XaBr — 2N - C0 2 + 2H 2 0. 

In the chapter on Reaction it was pointed out that urine when 
exposed to the air gradually undergoes ammoniacal fermentation, 
and that this decomposition is due to the action of a non-organized 
ferment, ammonia being liberated, according to the equation: 

CO< -f- H 2 = 2XH 3 - C0 2 . 

\*H 2 

The same decomposition may be effected by heating a watery solu- 
tion of urea in a sealed tube to 100° C. 

It might be supposed that an accurate estimation of urea could 
be made by adding a solution of the ferment, which can readily be 
obtained, to a known quantity of urine, and then determining the 
amount of ammonia liberated, 34 parts of the latter corresponding 
to 60 parts of urea. Unfortunately the complete decomposition of 
urea is obtained only with difficulty, so that the method is a very 
tedious one. The same objection, although to a less degree, can 
also be urged against the method commonly employed, viz., the 
hypobrornite method (which see), as 1 gramme of urea does not 
yield 372.7 c.c. of nitrogen, which would be theoretically required, 
but at the most only 354.3 c.c. 

Separation of Urea from the Urine. From 50 to 100 c.c. of 
urine are evaporated to a syrupy consistence upon a water-bath, 
and extracted with 100 to 150 c.c. of strong alcohol, by rubbing 
up the residue while still hot with the alcohol. Upon cooling, the 
mixture is filtered, the alcohol evaporated, and the residue treated 
with pure cold nitric acid. Urea nitrate then separates out either 
immediately or on standing. After twenty-four hours the crystal- 
line mass is collected upon a muslin filter, well strained, and freed 
from anv liquid by placing it upon plates of clay. It is then dis- 
solved in hot water, and the solution, if strongly colored, gently 
warmed with animal charcoal. This solution is neutralized with 



THE URINE. 335 

barium carbonate, and rendered alkaline with barium hydrate. 
The urea nitrate is thus decomposed, barium nitrate and urea 
being formed: 

2CON a H 4 .HNO a + BaC0 3 = 2CON,H 4 + Ba(N0 8 ) a + H 2 0. 

The barium is now removed by passing a stream of C0 2 through the 
solution and filtering off the precipitate. The filtrate is evaporated 
nutil any barium nitrate still remaining crystallizes out. This is 
removed by decantatiou, when upon further evaporation the urea 
crystallizes out, and may be dried between layers of filter-paper 
and recrystallized from 95 to 98 per cent, alcohol. The crystals 
thus formed may now be subjected to further tests. To this end 
a few drops of an aqueous solution are added to a few c.c. of a 
sodium hypobromite solution, when in the presence of urea bubbles 
of gas will be given off. ^Yith a solution of sodium hypochlorite the 
same result may be obtained, but in this case the evolution of gas 
only takes place upon the application of heat. The formation of 
biuret may also be demonstrated by carefully melting a few of the 
crystals in a test-tube, dissolving the residue, when cool, in a little 
water, and alkalinizing the solution with a little sodium hydrate; 
upon the addition of a drop or two of a dilute solution of sulphate 
of copper a beautiful reddish- violet color, owing to the presence of 
biuret, will develop. 

The addition of oxalic or nitric acid to a solution of urea will 
give rise to the formation of urea nitrate aud oxalate, as described 
above. 

This latter test may very conveniently be made under the micro- 
scope. A drop of the concentrated solution is placed upon a slide 
and covered, and a drop of pure nitric acid added from the side. 
( rvstals of urea nitrate will then be seen to separate out, and may 
be recognized by their characteristic shingle-like arrangement (see 
Fig. 79). 

When a urine is very rich in urea the mere addition of nitric acid 
will cause a more or less abundant precipitation of urea nitrate, and 
with this simple test an idea may even be formed of the amount 
present pro liter. An appearance of hoar-frost is thus only noted 
when not less than 25 grammes are present to the liter, while the 
formation of spangles of urea nitrate requires the presence of at 
least 45 grammes, and a heavy sediment is noted only when 50 
grammes or more are present. 



336 CLINICAL DIAGNOSIS. 

Quantitative Estimation of Urea. The only method which 
will be considered in detail is the one based upon the decomposi- 
tion of urea into carbon dioxide and nitrogen in the presence of 
sodinm hypobroniite, which reaction takes place according to the 
equation : 

OON 2 H 4 -f- 3NaOBr = NaBr + C0 2 -j- 2H 2 + 2N. 

The carbon dioxide thus formed is absorbed by an excess of sodium 
hydrate added to the hypobromite solution, while the nitrogen is 
set free, and can be suitably collected and measured, whence the 
determination of the corresponding amount of urea becomes a 
simple matter. 

The only solution that is necessary is one of sodium hypobromite 
containing an excess of sodium hydrate. A 30 per cent, solution 
of the latter should be kept on hand and the sodium hypobromite 
solution prepared when required. To this end 70 c.c. of the sodium 
hydrate solution are diluted with 180 c.c. of water and treated with 
5 c.c. of bromine in a bottle provided with a ground-glass stopper, 
the mixture being thoroughly shaken until every trace of free 
bromine has disappeared. Heat is evolved during this process, 
and the mixture should not be used until cold. The sodium hypo- 
bromite solution, if kept in a perfectly dark and cool place, may 
be preserved for a week or two. The reaction which takes place 
between the sodium hydrate and the bromine may be represented 
by the equation : 

2NaOH -f 2Br = JS'aBr + NaOBr -f H 2 0. 

Various forms of apparatus, termed ureometers, have been sug- 
gested for the estimation of urea by this method. One which the 
author has found very satisfactory is represented in Fig. 81. It 
consists essentially of a burette, C, with an ascending rubber tube 
attached to the reservoir B, which can be raised or lowered as 
required for the purpose of equalizing the pressure, after the col- 
lection of the gas in the burette. A descending tube leads to a 
wide-mouthed bottle, A, containing the hypobromite solution. 
This is closed by a tightly fitting rubber stopper, to which a loop 
of platinum-wire is attached carrying a little bucket made of glass 
or porcelain, which can be swung from its support by inclining the 
bottle. 

Method: The rubber stopper is removed from the bottle A, and 
water poured into B until the system BCA is filled to such an 



THE URINE. 



337 



extent that the water-level is visible iu B above the point where 
the rubber tube is attached. About 25 to 30 c.c. of the hypobro- 
mite solution are then placed in the bottle A, 5 c.c. of urine into 
the little bucket, and this attached to the wire loop. The stopper 
is then carefully adjusted aud the water in B and C brought to the 
same level, when the first reading is taken. A is then inclined 
until the little bucket drops into the liquid below. The nitrogen 
which is liberated collects in the burette C, the water falling in C 

Fig. 81. 




The author's ureometer. 



and rising in B. After twenty to thirty minutes the pressure in C 
is •■'pialized by lowering B until the water in both tubes has reached 
the same level. The second reading is then taken, the difference 
between the two indicating the volume of nitrogen liberated from 
5 c.c. of urine at the temperature of the water in CB, which, as well 
as the barometric pressure, should be previously noted. 

22 



338 CLTXICAL DIAGNOSIS. 

As the volume of gases is greatly influenced by the temperature, 
the barometric pressure, and the tension of the aqueous vapor, it 
lecornes necessary, in order that the results reached shall be com- 
parable with those obtained by other observers, to reduce the volume 
of nitrogen actually :_ :e ' :: eertain standard. This has been 
placed at C C. and 76'J mercury millimetres pressure, in the absence 
of moisture. This correction is made according to the following 

v p -r 

formula: V = — : — — — — — . in which V represents the cor- 

■y\ 1 — M.(jn:3t;»j.t L 

rected volume of the gas in terms of c.c v the volume actually ob- 

served. B the barometric pressure in Hgmm., T the tension of the 

aqueous vapor at the temperature noted, t. The volume of nitrogen 

".■■".'served being thus x>rrected, the ?alculation of the corresponding 

amount of urea is based upon the following considerations: From 

the formula COX.H. it is apparent that 2 atoms of nitrogen are 

contained in 1 molecule of urea: in other words, that 28 pans 

by weight of nitrogen :-orrespon:l : parts by weight of urea. 

The equivalent of 1 gramme of urea is then found according fx 

the equation: 60 : 28 : : 1 : x, and x = 0.46666. The volume 

corresponding to '"'.-:::■ gramme of dry nitrogen at : C. and 

~: ) Hgmm. pressure is 372.7 c.c. It has been found, however. 

that only 354.3 c.c. of nitrogen are evolved from 1 gramme of urea 

at best, when the hypobroniite method is employed. Knowing that 

354.3 c.c. of nitrogen correspond v: 1 gramme of urea, the amount 

of urea to which the volume of nitrogen actually observed is referable 

would then be found according to the equation: 1 : 354.3 : : x : y. 

and x= -^ — -j in which v denotes the number of c.c. of nitrogen 
354.3 

evolved from 5 c.c. of urine, and x the corresponding amount of 

urea. Io :: -: : ;■.- T.Tain the percental; -amount of urea.it is 

only necessary to multiply the figure just obtained by 20. 

Precautions: 1. The urine must be free from albumin. 2. It 
should contain only about 1 per cent, of urea — i. e.. not more than 
0.05 gramme in 5 c.c. corresponding to 17.715 to 20 c.c. of nitro- 
gen. Whenever a greater amount is noted, therefore, the urine is 
diluted to the proper degree, allowance being made in the calculation. 

In ordinary clinical work the barometric pressure, as well as the 
tension of the aqueous vapor, may be ignored, and in the tables 
appended the corresponding amount of urea may be directly read 
nperatures 5°, 10°, 15°, 20°, 25% and 30 c C. 



THE URISK. 



339 



Urea. Table for a Temperature of 5° C. 





1 
1.82 


1.45 


1.58 


3 / 10 




5 /io 


6 /io 


7 /io 


8 /io 


»/io 


1 


1.71 


1.85 


1.98 


2.11 


2.21 


2.37 


2.51 


2 


•J. 64 


2. 77 


2. HO 


3. 08 


3.17 


3.30 


3.43 


3.56 


3.69 


3.83 




8. 96 


4.00 


4.22 


4.36 


4. 49 


4.62 


4.75 


4.88 


5.02 


5.15 


•1 




i il 


5.54 


5. 68 


5.81 


5.94 


6.07 


6.20 


6.34 


6.47 




6.60 


6. 78 


6.87 


7.00 


7.13 


7.26 


7.39 


7.53 


7.66 


7.79 


6 


7. 92 


8.05 


8.19 


8.32 


8.45 


8.58 


8.71 


8.85 


8.98 


9.11 


7 


9. 24 


9. 38 


9.51 


9.64 


9.77 


9.90 


1<». 04 


10.17 


10.30 


10.43 


- 


10.56 


10. 70 


10. 83 


10. 96 


11.09 


11. 22 


11.36 


11.49 


11. 62 


11.75 


g 


11.89 


12.02 


12.15 


12. 28 


12.41 


12. 55 


12.68 


12.81 


12. 94 


13.07 


10 


18.21 


13.34 


13.47 


13. 60 


13.73 


13.87 


14.00 


14.13 


14.26 


14.39 


ii 


14.53 


14.66 


14.79 


14.92 


15.06 


15.19 


15. 32 


15.45 


15.58 


15.72 


12 


15.85 


15.98 


16.11 


16. 24 


16.38 


16.51 


16.64 


16.77 


16. 90 


17.04 


18 


17.17 


17. 30 


17. 43 


17.57 


17.70 


17.83 


17. 96 


18.09 


18.23 


18.36 


U 


IS. 49 


18.62 


18.75 


18.89 


19.02 


19.15 


19. 28 


19.41 


19.55 


19.68 


15 


1-.'. si 


19.94 


20.08 


20. 21 


20. 34 


20.47 


20.60 


20.74 


20.87 


21.00 


It". 


21.18 


21.26 


21.40 


21.53 


21.66 


21.79 


21.92 


23.06 


22. 19 


22. 32 


17 


22. -J.') 


23. ."'0 


22. 72 


22. 85 


22.98 


23.11 


23.25 


23.38 


23.51 


23.64 


18 


23. 77 


23.91 


24. 04 


24. 17 


24.30 


24.43 


24.57 


24.70 


24.83 


24.96 


19 


25. 10 


25. 23 


25. 36 


25.49 


25. 62 


25.76 


25.89 


26.02 


26.15 


26.28 


20 


26. 42 


26.55 


26. 68 


26.81 


26.94 


27.08 


27.21 


27.34 


27.47 


27.60 


Jl 


27.71 


■27. 87 


28.00 


28.13 


28.27 


28.40 


28.55 


28.66 


28.79 


28.93 


22 


29.06 


29. 19 


29. 32 


29.45 


29. 59 


29.72 


29.85 


29.98 


30.11 


30.25 


23 


30. SS 


30.51 


30.64 


30. 78 


30.91 


31.04 


31.17 


31.30 


31.44 


31.57 


24 


31.70 


31.83 


31.96 


32. 10 


32. 23 


32. 36 


32.49 


32.62 


32.76 


32. 89 


25 


33.02 


33.15 


33.29 


33.42 


33.55 


33.68 


33.81 


33.95 


34.08 


34.21 




34, 34 


34.47 


34.61 


34.74 


34. *7 


35.00 


35.13 


35.27 


35.40 


35. 53 


27 


35.66 


35.80 


35.93 


36.06 


36. 19 


36.32 


36.46 


36.59 


36.72 


36.85 


28 


36. 98 


37.12 


37.25 


37.38 


37.51 


37.64 


37.78 


37.91 


38.04 


38.17 


29 


38.31 


38.44 


38.57 


38.70 


38.83 


38.97 


39.10 


39. 28 


39.36 


39.49 


30 


39.63 


39.76 


39.89 


40.02 


40.15 


40. 29 


40.42 


40.55 


40.68 


40.81 



Urea. Table for a Temperature of 10° C. 





1 


Vio 


M0 


3 /io 


4 / 10 


5 /io 


6 /io 


7 /io 


8 /io 


9 /io 


1 


1.31 


1.43 


1..56 


1.69 


1.82 


1.95 


2.08 


2.21 


2.34 


2.47 


2 


2.60 


2.73 


2.86 


2.99 


3.12 


3.25 


3.38 


3.51 


3.64 


3.77 


3 


3.90 


4.03 


4.16 


4.29 


4.42 


4.55 


4.68 


4.81 


4.94 


5.07 


1 


5.20 


5.33 


5.46 


5.59 


5.72 


5.85 


5.98 


6.11 


6.24 


6.37 


5 


6.50 


6.33 


6.76 


6.89 


7.02 


7.15 


7.28 


7.41 


7.54 


7.67 


6 


7.80 


7.93 


8.06 


8.19 


8.32 


8.45 


8.58 


8.71 


8.84 


8.97 


7 


9.10 


9.23 


9.36 


9.49 


9.62 


9.75 


9.88 


10.01 


10.14 


10.27 


s 


10.40 


10.53 


10.66 


10.79 


10.92 


11.05 


11.18 


11.31 


11.44 


11.57 


9 


11.71 


11.84 


11.97 


12.10 


12.23 


12. 36 


12. 49 


12.62 


12.75 


12.88 


10 


13.01 


13.14 


13. 27 


13.40 


13.53 


13. (\6 


13. 79 


13. 92 


14.05 


14.18 


11 


14. 30 


14.44 


14.57 


14.70 


14.83 


14. 95 


15.09 


15.22 


15.35 


15.48 


12 


15.60 


15. 74 


15. 87 


16.00 


16.13 


16.26 


16.39 


16. 52 


16.65 


16.78 


13 


16.91 


17.04 


17.17 


17.30 


17.43 


17. 56 


17.69 


17.82 


17.95 


18.08 


14 


is Jl 


18.34 


18.47 


18.60 


18. 73 


18.86 


18.99 


19. 12 


19.25 


19. 38 


is 


19.51 


19.64 


19.77 


19.90 


20.03 


20.16 


20. 29 


20. 42 


20.55 


20.68 


16 


20.81 


20.94 


21. 07 


21.20 


21.33 


21.46 


21.59 


21.72 


21.85 


21.98 


17 


22.11 


22.24 


22. 37 


22.50 


22.63 


22. 76 


22. 89 


23.02 


23. 15 


23. 28 


is 


23.41 


23.54 


23.67 


23.80 


23.93 


24.06 


24.19 


24.32 


21.45 


24.58 


19 


24.72 


24.85 


24.98 


25. 11 


25. 24 


25.37 


25.50 


25.63 


25. 76 


25. 89 


20 


26. 02 


26.15 


26. 28 


26. 41 


26.54 


26.67 


26.80 


26.93 


27.06 


27.19 


21 


27. 32 


27. 15 


27.58 


27.71 


27.84 


27.97 


28.10 


28.23 


28.36 


28.49 


22 




28.75 


28.88 


29.01 


29.14 


29. 27 


29.40 


29.53 


29.66 


29.79 




29.92 


30. 05 


3U.18 


30.31 


30.44 


30. 57 


30.70 


30.83 


30.96 


31.09 


24 


31.22 


31. 35 


31.48 


31.61 


31.74 


31.87 


32. 00 


82. 13 


32.26 


32.39 


25 




32. 65 


32. 78 


32.91 


33.01 


33. 17 


33. 30 


33. 43 


33.56 


33. 69 


26 


33.82 


33.95 


34.08 


34 21 


34.31 


34.47 


34.60 


34.73 


34.86 


34.99 


j 7 


35. 12 


35.25 


35.38 


35.51 


35.64 


35. 77 


35.90 


36. 03 


36.16 


36. 29 


28 


36.42 




36.68 


36.81 


36.94 


37.07 


37.20 


37.33 


87.46 


37.59 


2:> 


37.73 


37.86 


37. 99 


3S. 12 


38. 25 


38.38 


38.51 


38.64 


38.77 


38.90 


30 


39.03 


39.16 


39.29 


39.42 


39.55 


39.68 


39.81 


39.94 


40.07 


40. 20 



340 



CLiyiCAL LI A GXOSIS. 



Urea. Table fob a Temperature of 1o : C. 



1 


%■ 


%o 


%a 


^10 


5 fto 


: : 


:: 


= :: 


9 /io 


1 


1.28 


1.41 


1.53 


1.33 


1.79 


1.92 


2.04 


217 


230 


243 




2.56 


2.69 


2.81 


2 34 


3.07 


3-20 


3. 33 


3.46 


3 . 3- 


n 


3 


3 ; 4 


3.97 


4.10 


i 2j 


4.35 


4 4" 


4.61 


4.74 


4.-7 


4.99 


4 


5.12 


:.i: 


3.3-S 


5.50 


5.63 


5.76 


5.89 


6.02 


6.14 


6.27 


: 


6.40 


6.53 


■?.•:: 


6.79 


6.91 


7.04 


7.17 


7.30 


' s 


7.55 


6 


7.68 


7.81 


" H 


^ ~ 


5 13 


8.32 


-.45 


S.5S 


8.71 


S.S3 


" 


3.96 


9.09 


9.22 


9.35 


?. 45 


9.61 


9.73 


3. s3 


9.99 


10.12 


5 


10.24 


10.37 


10.50 


i:.:3 


13. '3 


i:.s- 


11.01 


11.14 


11.27 


11.4: 


9 


11.53 


::.■:■:■ 


11.75 


11.91 


12. 34 




1229 


12 42 


12. -S 


12.- 


10 


:.. si 


12 93 


I:: a 


13.19 


13. 32 


13.45 


13. 57 


13.70 


13, B3 


13 96 


11 


14.09 


14.22 


14.34 


14.47 


14.-: 


14. 7? 


14.-: 


14. 9S 


15. 11 


15. 24 


12 


15. 37 


15.50 


:.-.-:: 


15. 75 


:•: i; 


i:i :i 


16.14 


16.26 


16.39 


16. 52 


13 


16.65 


i- 3 is 


16.91 


17.03 


17.16 


17.2? 


17. 42 


17. 55 


17 ' 


i7.s:- 


14 


17.93 


:s. :-: 


S 1 


if.?.: 


18.44 


1- :' 


18-70 


IS. S3 


:s?: 


lr.- 


15 


19.21 


lr. 34 


19.47 


13.3: 


1 72 


s ss 


13. 35 


20.11 


2:._4 


2:.s- : 


16 


:. s 


20.62 


20. 75 


_: . s- 


21.00 


21. 13 


21.26 


21.39 


21. 52 


21.64 


17 


.: 77 


:: v. 


::. :• 


::.:■: 


22 :? 


... 41 




... -7-7 


22.-: 


22 93 


is 


23.05 


:-: is 


23.31 


23.44 


23. 57 


23.62 


2--.S2 


s.s-- 


24. JS 


24.21 


19 


24. 34 


24. -:■: 


-4. "3 


14. "- 


24. S: 


14 :•- 


s :: 


s s 


25.36 


2:-. 4? 


:: 


:-:.-:: 




- -7 


26.00 


13. li 


26.26 


:~.?.s 


s. r l 


21. r4 


-: "- 


21 


26.90 


27.03 


27. 15 




27.41 


27.-54 


.- - 


27.79 


27 . 


28.05 


■>-> 


23.1- 


is.s: 


-V 43 


.s v. 


-S.~? 


:-. 52 


2-. ?:■ 


:•:. ;- 


29.20 


29.33 


23 


S-S 


29.59 


29.72 


2—4 


13. 37 


30.10 


30.23 


■z:.S'. 


33.43- 


30.61 


24 


30.74 


?■: -~ 


31.00 


31.12 


31.25 


s: 3-- 


31. 51 


31.64 


31. 76 


31.89 


25 


:. :_ 


32.15 


S2. .- 


32.41 


32.53 


-.. - 


£.."- 


32 92 


?-■ . : : 


33.17 


26 


n. i: 


33.43 


33.36 


3 : t3 


33.81 


3: ?i 


M - 


34.20 


34.33 


34.45 


'.- 


M 18 


34.71 


34. -4 


- 7 


35.10 


35. 42 


35. 35 


33.4- 


35.61 


35.74 


28 


3 r . S-? 


35.99 


36.12 


36.25 


"f.SS 


36.50 


iz.zc- 


36.76 


>:.-■ 


37.02 


2- 


37.15 


■- 27 


37.40 


37. 53 


37.66 


S - 


37.91 


3-. :-4 


38.17 


38.30 


so 


35 4c 


B8.5S 


3- 3- 


3$. SI 


35 34 


s. :: 


39.12 


: :: 


39. 45 


33. : s 



Urea. Table foe a Temperature of 20° C. 





1 


1{ 10 


2 io 


:: 


1 71 


1.89 




-.. 


! :: 


u 


1 


1.26 


::■ 


1.51 


L63 


2.01 


2.14 


2 26 


2.39 


1 




2.3. 


-- 


2.90 


?.:: 


3.16 


3 -' 


3.40 


3.53 




3 


3.7S 


3.91 


4.:: 


4.13 


4.2s 


4.41 


4.54 


4 -. 




4.91 


4 


5.04 


5.17 


5.29 


5 S. 


5.54 


:.-" 


:.-:■ 


5.92 


■ : :? 


6.17 


5 


6.30 


3.43 


6.55 


3 :s 


:.S1 


3.33 


7.06 


7.18 


7.31 


-.-14 


6 


".:- 


7.6? 


7.81 


" M 


S.37 


-.13 


-. : .2 


8.44 


8 57 


8.70 


7 


S.S2 


s 3: 


9.03 


9.20 


9.33 


9.45 


9.^ 


9.71 


183 


9.96 


8 


13.35 


i: 2i 


i:.34 


13.43 


1: V : 


10.71 


13.-4 


10 97 


11 3? 


11.22 


9 


11.35 


11.47 


1L60 


11.72 


11.85 


11 - 


12.10 


1223 


12.35 


1- « 


10 


12.61 


12.73 


12. S3 


12.- 


13.11 


13.24 


13.36 


13.49 


13.61 


13.74 


11 


i -■ 


13 99 


14.12 


14.25 


1453 


14.50 


14.62 


14 7" 


14 SS 


15.00 


12 


15.13 


15.25 


IT. 3- 


15.51 


15.63 


15.76 


:•: ; - 


16.01 


16.14 


16.26 


13 


16.39 


16.52 


16.64 


16.77 


I-:.-? 


17.:: 


17.15 


17.27 


17.40 


17.52 


14 


17.65 


17 -i 


17.90 


1S.33 


18.15 


1-.2- 


1- 41 


IS ^ 


1-.3-3 


1S.7S 


IS 


ISrl 


19.04 


lr.13 


19.29 


19.42 


19.54 


13.37 


19.79 


19.92 


_:.: T 


16 


.: i: 


20.30 


_: 42 


20.55 


2:.-:> 


23 -J 


_:.3? 


11 S 


2L18 


• 21.31 


17 


21.43 


2L56 


21.69 


21.81 


21.94 


22. '3 


2219 


22 :. 


22.44 


22.57 


18 


2269 


12 ij 


22.95 


23.07 


23.20 


23.32 


23.45 


23.5:3 


23.70 


23.83 


19 


23.33 


24 :s 


24.21 


24.33 




24.59 


24 71 


24.-4 


24.96 


25.09 


20 


.: a 


25.34 


25.47 


25 5? 


25.72 


25.85 


25.97 


2-m: 


1 22 


26.35 


21 


23.4- 


_: 3 : 


_ 71 


2'. S3 


23.3- 


27.11 


27.23 


27.36 




27 


22 


-" 74 


--.S-" 


27.99 




-3 2. 


2- 37 


2- 4/ 


a e 


2 ; 75 


.:- -■■ 


23 


29.00 


29.13 


S.S 


-V.c-S 


29.50 


s •: : 


29.76 


23.-- 


30.01 


?:•. 13 


24 


::: 2: 


30.39 


3051 


30.64 


30.76 


?:.S3 


31.02 


31.14 


: : 2: 


31^9 


25 


31.52 


31. -3" 


31.77 


31.90 


32 : ; 


32.15 


32 28 




32 -53 


3..-:- 


26 


3278 


32 91 


33.03 


33.16 


33.29 


33.41 


33.54 


33 66 


33.79 


: : - 


27 


34.04 


34.17 


34.30 


34.42 






S4.-: 


:,. : :- 


3 r .;: 


35.1s 


28 


3530 


35.4:3 


35.56 


?.:..3S 


35.81 


35.93 


36.06 


36.19 


36.31 


36.44 


29 


36.57 


36.69 


::.S: 


36 94 


37.07 


37/20 


37.32 


37.45 




■- - . 


30 


" -; 


37.95 


?-S.3'S 


?s._: 


3-3: 


3-43 




3- r s 


33.71 


3--.-: ? . 


3S.96 



THE URINE. 



341 



Urea. Table for a Temperature of 25° C. 






1.24 


1 10 

L.86 


- 10 


3 /l0 


4 /io 
1.73 


5 /,o 
1.86 


°/io 
1.98 


2.11 


8 /io 




1 


1.49 


1.61 


2 23 


2.35 


2 


2.48 


2.60 


2.78 


2.85 


2.97 


3.10 


3.22 


3 35 


3.47 


3.59 


3 


8.72 


3.84 


3.97 


4.09 


4.22 


4.34 


1. 16 


4.59 


4.71 


4.84 


4 


4.% 


5.08 


5.21 


5.83 


5 46 


5.58 


5.70 


5.83 


5.95 


6.08 


5 


6.20 


6 33 


6. l". 


6.57 


6.70 


6.82 


6.95 


7.07 


7.19 


7.32 


6 


7.44 


7.67 


7.69 


7.81 


7.94 


8.06 


8.19 


8.31 


8.43 


S.50 


7 


B68 


8.81 


B.98 


9.06 


9 18 


9.30 


9 43 


9.55 


9.68 


9.80 


< 


9.92 


10.05 


10.17 


10.30 


10.42 


10.54 


10.67 


10.79 


10.92 


10.04 


9 


11.17 


11.29 


11.41 


11.54 


11.16 


11.79 


11.91 


12.03 


12.16 


12.28 


10 


12.41 


12.53 


12.65 


12.7S 


12.90 


13.03 


13.1.") 


13.27 


13.40 


13.52 


11 


13.65 


13.77 


13.89 


14.02 


14.14 


14.27 


14.39 


14.52 


14.64 


14.76 


12 


14.89 


15 01 


15.14 


15.26 


15.38 


15.51 


15 63 


15.76 


15.88 


16.00 


13 


16.13 


16.25 


16.88 


16-50 


16.63 


16.75 


16.87 


17,00 


17.12 


17.26 


11 


17.37 


17.49 


17.62 


17.74 


17.87 


17 99 


18.11 


18.24 


18.36 


18.49 


15 


18.61 


18.74 ■ 


18.86 


18.98 


19.11 


19.23 


19.36 


19.48 


19.60 


19.73 


16 


19.85 


19.98 


2< .10 


20.22 


20.35 


20.47 


20.60 


20.72 


20.84 


20.97 


17 


21.09 


21.22 


21.84 


21.47 


21.59 


21.71 


21.84 


21.96 


22.09 


22.21 


18 


22.33 


22.46 


22.58 


22.71 


22.83 


22.95 


23.08 


23.20 


23.33 


23.45 


19 




23.70 


23 82 


28.9i 


24.07 


24.20 


24.32 


24.44 


24.57 


24.69 


20 


2 i B2 


24.94 


25.06 


2."). 19 


25.31 


25.44 


25.56 


25.68 


25.81 


25.93 


21 


26.06 


26.18 


26 30 


26-43 


26.55 


20.68 


26.80 


26.92 


27.05 


27.17 


22 


27.30 


27.42 


27.:-:. 


27.67 


27.79 


27.92 


28.04 


28.17 


28.29 


28 41 


23 


28 5 1 




28 7'.' 


2S.91 


29.04 


29.16 


29 28 


29.41 


29.53 


29.66 


24 


29.78 


29.90 


30.03 


30.15 


30.28 


30.40 


30 52 


30.65 


30.77 


30.90 


25 


31.02 


31.15 


31.27 


31 39 


31.52 


31.64 


31.77 


3189 


32.01 


32 14 


26 


32.26 


32.39 


32.51 


32 63 


32.76 


32.88 


33.01 


33.13 


33.25 


33.38 


27 


33.50 


33.63 


33.75 


33.88 


34.00 


34.12 


34.25 


34.37 


34.50 


34.62 


2S 


31.74 


34.87 


34.99 


35.12 


35.24 


35.36 


35 49 


35.61 


35.74 


35.86 


29 


35.99 


36.11 


36.23 


36.36 


36.48 


36 61 


36.73 


36.85 


36.98 


37.10 


30 


37.23 


37.35 


37.47 


37.60 


37.72 


37.85 


37 97 


38.09 


38.22 


38.24 



Urea. Table for a Temperature of 30° C. 






l ho 


MO 


1.22 


1.34 


1.46 


2.44 




2.68 


3.66 


3.78 


3.90 


4.88 


5 00 


5.12 


6.10 


6.22 


6 35 


7.32 


7.11 


7.57 


8.54 


8.67 


-.7'.' 


9 76 


9.89 


10.01 


10.99 


11 11 


11.23 


12.21 


12.33 


12.45 


13.43 


13.55 


13.67 


14.65 


11.77 


14.89 


15. s7 


15.99 


16.11 


17.09 


17.21 


17.33 


18.31 


18.48 


18.56 


19.53 


19.65 


19.78 


•in.::. 


2 - 


21 00 


21.97 


22.10 


22 22 


23.19 


23.32 


23 44 


24.42 


21 5 1 


24.66 












27.10 


28.08 


28.20 


28.32 


29 30 


2'.'. 12 


29.54 


30.52 


30.64 


30.77 


31.74 




81.99 


32.96 


33.09 


33.21 


34.18 


34.31 


34.43 


35.41 


35.53 


85 65 


36.63 


36.75 


36.87 



3 /l0 



1.58 

2.80 

4.03 

5.25 

6.47 

7.69 

8.91 

10.13 

11.35 

12.57 

13.79 

15.01 

16.24 

17,16 

18.68 

19.90 

21.12 

22.^1 

23.56 

24.78 

26.00 

27.22 

28.4 i 

29.67 

30.89 

32. 1 1 

33.33 

34.55 

35.77 

36.99 



4 /io 



171 
2.93 
4.15 
5.37 
6.59 
7.81 
9.03 
10.25 
11.47 
12 69 
13.92 

loll 

16.36 
17.58 
18.80 
20.02 
21.24 
22.46 
23.68 
24.90 
26.13 
27.35 
28.57 
29.79 
31.01 
32.23 
33.45 
34.67 
35.89 
37.11 



''"in 



1.83 

3.05 

4.77 

5.49 

6.71 

7.93 

9.15 

10.37 

11.60 

12.82 

14.04 

15.26 

16.48 

17.70 

18.92 

20.14 

21.3S 

22.58 

23.81 

25.03 

26.2.". 

27.47 

28.69 

29.91 

31.13 

32.35 

33.57 

34.79 

36.02 

37.21 



1 

6 /l0 


7 /io 


8 /l0 


9 10 


1.95 


2.07 


2.19 


2.32 


3.17 


3.29 


3.41 


2.54 


4.39 


4.51 


4 64 


4.76 


561 


5.73 


5.86 


5.98 


6.83 


6.96 


7.08 


7.20 


8.05 


8.1S 


8.30 


8.42 


9.28 


9.40 


9.52 


9.64 


10.50 


10.62 


10.74 


10.86 


11.72 


11.84 


11.96 


12.08 


12.94 


12.06 


13.18 


13.30 


14.16 


14.28 


14.40 


14.53 


15.38 


15.50 


15.62 


15.75 


16.60 


16.72 


16.85 


16.97 


17.82 


17.94 


18.07 


18.19 


19.04 


19.17 


19.29 


19.41 


20.26 


20.39 


20.51 


20.63 


21.49 


21.61 


21.73 


21.85 


22.71 


22.83 


22.95 


23.07 


23.93 


24.05 


24.17 


24.29 


25.15 


25 27 


25.39 


25.51 


26 37 


26.49 


26 61 


26.74 


27.59 


27.71 


27.83 


27.96 


28.81 


28.93 


29.06 


29.18 


30.03 


30.1.-) 


30.28 


30.40 


31.25 


31.38 


31.50 


31.62 


32 47 


32 60 


:12.72 


32.84 


33.70 




33.94 


34.06 


34.92 


85.04 


35.16 


35 28 


36.14 


36.26 


36.38 


36 50 


37.36 


37.48 


37.60 


37.72 



342 



CLINICAL DIAGNOSIS. 



Fig. 82. 



Of the other forms of apparatus, the ureouieters devised by Dore- 
nms, Green, Marshall, Hiiffner, and Squibb may be mentioned. 

The^latest modification of Dorernus' apparatus is certainly most 
convenient, and can be highly recommended. Its general construc- 
tion is seen in Fig. 82. A small amount of urine is poured into B 

while the stopcock (C) is closed. 
This is then opened for a moment 
and again closed, so as to fill its 
lumen. The tube (A) is washed out 
with water and filled with the hy- 
pobromite solution. The tube (B) is 
filled with urine, when 1 c.c. or less, 
if the urine is concentrated, is al- 
lowed to mix with the hypobromite 
solution in A. After all bubbles of 
gas have disappeared the reading is 
taken. The degrees marked upon the 
tube indicate directly the number of 
grammes or grains of urea contained 
in the amount of urine employed. 1 

Green's apparatus (Fig. 83) con- 
sists of a tube graduated in c.c, 
and blown out at the bottom into 
a wider portion, holding about 50 to 
60 c.c. The bulb is provided with 
a side-tube, into which a bent funnel- 
tube can be inserted for the purpose 
of equalizing the pressure. The side- 
tube having been detached, the appa- 
ratus is filled with sodium hypobro- 
mite solution, when 2 c.c. of urine, diluted if necessary, are in- 
troduced by means of a graduated and bent pipette. After all 
bubbles of gas have disappeared the funnel-tube is inserted into the 
side-opening and filled with hypobromite solution until the level in 
both tubes is the same. The volume is then noted, corrected, and 
the corresponding amount of urea calculated as described. 




Doremus' ureometer. 



i Instead of employing the solution described on page 336, it is sufficient to fill the long 
arm of the tube with a solution containing 100 grammes of caustic soda dissolved in 250 c.c. 
of distilled water, and to add 1 c.c. of bromine and a sufficient amount of water to fill the 
bend of the tube. 



THE URISi:. 



:)\:\ 



Marshal? $ apparatus is a conveniently modified form of Green's, 
and is used in the same manner (Fig. 84). 

Hiiffner's apparatus is excellent (Fig. 85). It consists of a small 
bulb, A, of 5 c.c. capacity, which is separated from a larger bulb, 

C, holding about 100 c.c, by a well-oiled glass stopcock. The 
upper end of C is drawn out to such an extent that the eudiometer 

D, which is about 30 cm. long, 2 cm. wide, and divided into fifths 
of c.c, can be passed over it for a short distance. The bowl E, 
fitted over C by means of a cork, serves to hold a portion of the 
hypobromite solution. 

The exact capacity of A and of the lumen of the stopcock must 
be separately determined for each instrument. 

Method: The bulb A and the lumen of the stopcock are filled 
with urine which has been diluted, if necessary. The stopcock 
having been closed, C is washed out carefully with distilled water 
and tilled with the hypobromite solution until the liquid in the 



Fig. 83. 



Fig. 84. 



Fig. 85. 




Green's ureometer. 



Marshall's ureometer. 



Hiiffner's ureometer. 



dish stands several cm. above the mouth of C. The eudiometer is 
next filled with the same solution and carefully submerged in the 
liquid contained in the dish, adjusted over the mouth of C. The 



344 



CLINICAL DIAGNOSIS. 



urine in A is then allowed to mix with the hypobromite solution 
very gradually by opening the stopcock. After all bubbles of gas 
have disappeared the eudiometer is transferred to a cylinder filled 
with water and thoroughly immersed. After twenty to thirty 
minutes the level of the liquid in the tube and that of the outside 
water are equalized and the reading taken. The temperature of 
the water being likewise noted, the volume of the gas is corrected 
and the corresponding amount of urea calculated. 

Squibb' s method: This method, like that of Doremus, may 
be highly recommended to the practitioner for its simplicity. The 
apparatus (Fig. 86) consists of two ordinary medicine-bottles, A 
and B, A being the one in which the nitrogen is evolved. B is 
closed by a doubly perforated rubber-stopper, a straight tube pass- 



FlG. 86. 




Squibb' s ureometer. 



ing through the upper aperture and connecting with the bottle A. 
Another tube, bent downward and carrying a clamp, as seen in the 
figure, leads to a graduated cylinder, E. B contains a sufficient 
amount of water for the bent tube to dip into; 25 to 30 c.c. of the 
hypobromite solution, and a small tube containing 5 c.c. of urine, 
diluted if necessary, according to the specific gravity, are placed in 
A, the clamp at E being closed. The rubber-stopper is now firmly 
inserted and E opened, when a few drops of water, which may be 
disregarded, will escape. The graduated cylinder is then placed 
beneath the outflow-tube and the bottle A inclined. The nitrogen 
collecting in B displaces its own volume of water, which flows out 



THE URINE. 



345 



and is collected in E, whence the corresponding amount of urea 
may be calculated. 

It should be mentioned that sodium hypobromite liberates nitro- 
gen, not only from the urea, but also from the other nitrogenous 
constituents of the urine; the error thus incurred, however, appears 
just to counterbalance the deficit in the amount of nitrogen obtained, 
corresponding to 1 gramme of urea. 

Estimation of Nitrogen. For the purpose of estimating the 
total amount of nitrogen in the urine, the method of Kjeldahl or 
that of Will-Varrentrapp is most conveniently employed. 

KjeldahPs method: Principle : The organic material of the urine 
is decomposed by means of sulphuric acid, when all the nitrogen 



Fig. 87. 





Kjeldahl's nitrogen apparatus. 



which is not present in combination with oxygen is transformed 
into ammonia. After adding sodium hydrate in excess this is then 
• li-tilled off and received in a known quantity of titrated acid, the 
excess being retitrated with sodium hydrate. In this manner the 
amount of ammonia and the corresponding quantity of nitrogen is 



346 CLINICAL DIAGNOSIS. 

ascertained, it being remembered that 17 grammes of ammonia 
correspond to 14 grammes of nitrogen. 
Reagents required: 

1. Gunning's mixture. This consists of 15 c.c. of concentrated 
sulphuric acid, 10 grammes of potassium sulphate, and 0.5 gramme 
of copper sulphate. 

2. A solution of sodium hydrate containing 270 grammes in the 
liter (sp. gr. 1.243). 

3. Pulverized talcum or granulated zinc. 

4. A one-fourth normal solution of sulphuric acid. 

5. A one-half normal solution of sodium hydrate. 
Apparatus required (see Fig. 87). This consists of a retort of 

about 750 c.c. capacity (A), which is connected with a Kjeldahl 
distilling tube (B), and through this with a Stadeler's condenser 
(C). The ammonia is received in the nitrogen bulb at D. 

In addition a Kjeldahl digesting flask of 200 to 300 c.c. capacity 
is required. 

Method: 5 or 10 c.c. of urine are placed in the digesting flask 
and treated with Gunning's mixture. To this end it is best to add 
the sulphuric acid and copper sulphate first, to heat until sulphuric 
acid vapors are given off in abundance, and then to add the potas- 
sium sulphate. The heating is contiaued until the solution has 
become entirely clear and almost colorless, the flask being inclined 
to an angle of about 45°. Vigorous ebullition should be avoided. 

Upon cooling the contents of the flask are washed into the retort, 
using as little water as possible, and slowly treated with a moderate 
excess of the sodium hydrate solution. As a general rule, 40 c.c. 
for every 5 c.c. of sulphuric acid are sufficient. A little pulverized 
talcum or a few pieces of granulated zinc are finally added, when 
the retort is connected with the condenser, and the distillation 
begun. This is continued until about two-thirds of the solution 
have passed over. The distillate is received in the nitrogen bulb, 
which should contain a carefully measured quantity of the one-fourth 
normal solution of sulphuric acid. As a general rule, 30 c.c. are 
sufficient. As soon as the distillation is completed the condenser 
is disconnected, washed out with a small amount of distilled water, 
and the washings added to the distillate. After the addition of 
a few drops of tincture of cochineal, the excess of sulphuric acid 
is then retitrated with the one-fourth normal solution of sodium 
hydrate, and the amount found deducted from the 30 c.c. used. 



THE URINE. 



347 



The titration should be continued until every trace of yellow has 
disappeared and a pare rose-color is obtained. The difference 
multiplied with 0.0035 will then indicate the amount of nitrogen 
present in the 5 or 10 e.e. of urine. The corresponding amount 
of urea is found by multiplying this figure with 20. 

A- lvjeldahl's method presupposes a thorough knowledge of 
chemical technique, it is well to make at least two parallel esti- 
mations in every case. 

Will-Yarrentrapp' s method, as modified by Seegeu -Schneider. 
Principle: If nitrogenous organic material is heated in intimate 
contact with soda-lime, all the nitrogen is given off in the form of 
ammonia, which is collected in a known quantity of acid; the excess 

e ' Fig. 88. 




Apparatus for the determination of nitrogen. 

not used in the neutralization of the ammonia is then determined 
by titratiou with a solution of sodium hydrate of known strength. 
The amount held by the ammonia is thus ascertained, and from it 
the corresponding amount of nitrogen, it being remembered that 17 
grammes of ammonia correspond to 14 grammes of nitrogen. 

Reagents required: 1. A quantity of thoroughly fused calcic 
soda, which, while still hot, should be placed in a well-stoppered 
bottle, where it may be kept ready for use for a long time. 



348 CLIXICAL D1AGX0SIS. 

2. A normal solution of sulphuric acid. 

3. A normal solution of sodium hydrate. 

Apparatus required: As is apparent from the preceding diagram 
Fig. 88 . the apparatus consists of a Kjeklahl digesting flask. A. 
provided with a long neck (10 to 12 cm. long\. of about 100 c.c. 
capacity, which is placed in a copper erucet. B. and imbedded in 
-and. The erucet is placed upon a pipe-stem triangle over the 
Same. The neck of the flask is surrounded by a hood of copper 
or tin plate. C, moulded to the flask and reaching not higher than 
1.5 cm. below the rubber-stopper. The latter is doubly perforated, 
a tube c drawn out to a point and closed at the free end passing* 
through one aperture and extending about half-way down the flask 
while the second passes through the other opening. This second 
tube, c, is connected by means of a short piece of robber-tubing, 
upon which a clamp is placed, with a "Will-Varrentrapp apparatus. 
The latter is connected by rubber-tubing, upon which a clamp is 
likewise placed, with an aspirating-bottle filled with water, into 
which a siphon, provided with a rubber-tube at its free end. dips 
to the bottom. 

Method: Ten c.c. of the normal sulphuric-acid solution are placed 
in the Will-Varrentrapp apparatus together with a few c.c. of 
a 1 per cent, solution of phenolphtkalein. A layer of -and about 
1 cm. in height is placed in the erucet. the clamp a closed, and the 
flask filled to about one-half its height with the soda-lime, when the 
hood is adjusted and 5 c.c. of urine allowed to flow upon the soda. 
The robber-stopper is quickly adjusted, the robber tube having 
been previously connected with the Will-Varrentrapp apparatus. 
The clamp a is now opened, the erucet filled up with sand, and the 
heating begun. This is at first done carefully with a small flame. 
but increased gradually until a full heat is applied. This is con- 
tinued for cine-half to three-quarter- of an hour. When drops of 
moisture are no longer visible in the tube e, or when the evolution 
of gas has entirely ceased, the rubber-tube of the aspirating-bottle 
d is slipped on to the Will-Varrentrapp apparatus, the clamp b 
-lightly opened, the tip of t broken off. and air allowed to pass 
slowly through the entire system for a quarter of an hour, when 
the flame is extinguished. The Will-Varrentrapp apparatus is 
then detached, and its contents titrated with the normal solution of 
sodium hydrate. 

The number of c.c. of the sodium hydrate solution employed is 



THE URINE. 349 

deducted from in (the number of e.c. of the normal sulphuric-acid 
solution, 1 o.c. of the latter being equivalent to 1 e.c. of the for- 
mer), the difference giving the number of e.c. of the normal sul- 
phuric-acid solution neutralized by the ammonia evolved from 5 
e.c. of urine. This number multiplied by 20 will then represent 
the number of c.e. required to neutralize the ammonia contained in 
100 e.c. of urine. As 1000 e.c. of the normal solution of sulphuric 
acid correspond to 17 grammes of ammonia or 14 grammes of nitro- 
gen, the number of e.c. of the sulphuric-acid solution corresponding to 
LOO c.c. of urine will be found from the equation: 1000 : 14 : : x : y, 
and y = 0.014 x, in which x represents the number of c.c. required 
to neutralize the amount of ammonia evolved from 100 c.c. of urine 
and y the corresponding amount of nitrogen — i. e. } the percentage 
of nitrogen. 

If the nitrogen is to be calculated in terms of urea, this is done 
according to the equation: 1000 : 30 (= 14X) : : x : y, and y = 
0.03 x = percentage of urea, in which x represents, as above, the 
number of c.c. of sulphuric acid neutralized by the ammonia, viz., 
nitrogen, contained in 100 c.c. of urine, and y the urea correspond- 
ing to this amount. 

Uric Acid. 

1 Iric acid was formerly regarded as an antecedent of urea, but this 
view has now been abandoned. 

In the case of birds the researches of Minkowski, v. Schroeder, 
and others seem to point to an origin of uric acid analogous to 
that of urea in mammals. A great decrease in the elimination of 
this substance has thus been observed after extirpation of the liver 
in geese, which was associated with a corresponding increase in the 
excretion of ammonia and of lactic acid. In mammals uric acid is 
apparently derived from nuclein by a process of dissociation, and 
the spleen has recently been suggested as the most probable seat of 
its formation. As a matter of fact, an increased elimination has 
been observed in cases of splenic hypertrophy, which disappeared 
again, as the size of the organ returned to the normal, under the 
administration of quinine. The observations of Horbaczewski, 
moreover, who noted a decided new formation of uric acid when 
blood of calves and splenic pulp were allowed to stand in contact 
in the presence of oxygen, appear to render the splenic origin of 
this substance still more probable. The leucocytes are thought to 



350 CLINICAL DIAGNOSIS. 

be especially concerned in this transformation, and, as a matter of 
fact, it is known that the amount of uric acid is increased in cases 
of splenic leukaemia and during the process of digestive leucocytosis. 
The origin of uric acid from nuclein is also well shown in the fact 
that the ingestion of food containing much nuclein, such as thymus 
gland, leads to an increased elimination, while during a milk-diet 
minimal amounts only are excreted. 

Uric acid, which is almost insoluble in water, is held in solution 
in the urine in consequence of the presence of disodium phosphate, 
which transforms it into the readily soluble neutral disodium urate, 
according to the following equation: 

2Na 2 HP0 4 + C 5 H 4 N 4 3 = 2NaH 2 PO,+ C 5 H 2 Na 2 N 4 3 . 

Should uric acid be present in larger amount, the disodium urate 
gives up part of its sodium, acid monosodium urate resulting, 
which, being soluble with difficulty, is thrown down in concentrated 
urines as a sediment. The reaction taking place is represented by 
the following equation: 

C 5 H 4 N 4 3 + C 5 H 2 Na 2 N 4 3 - C 5 H 3 NaN 4 3 + C 5 H 3 NaN 4 3 . 

Should a still greater amount of uric acid be present, this is thrown 
down as such. 

The normal amount of uric acid excreted in the twenty-four 
hours may be said to vary between 0.2 and 1 gramme, being 
influenced to a certain extent by the character of the food, a 
diet rich in nitrogenous material increasing the amount of uric 
acid, while a diminished elimination of uric acid results from a 
diet free from nitrogen. It is also influenced by the amount of 
exercise taken, diminishing during rest and increasing with mus- 
cular activity. In addition, there are certain individual peculiari- 
ties, of the nature of which, however, practically nothing is known. 
Hence it has always been held that it is impossible in many cases 
to state definitely whether the amount of uric acid excreted by an 
individual is normal or not, as the tolerance on the part of the body 
of this substance varies greatly in different persons. 

The relation normally existing between the excretion of uric acid 
and of urea has been placed at between 1 : 50 and 1 : 60, but is in- 
constant, especially in pathologic conditions, in which the relative 
amount of uric acid may be greatly increased. It is impossible, 
however, at the present time to furnish a satisfactory explanation 
of the variations in the excretion of uric acid observed in patho- 



THE URINE. 351 

Logic conditions, and but little more, in fact, can be done than to 
enumerate the various diseases in which such variations have been 
observed. 

In febrile diseases, as typhoid fever, pneumonia, pleurisy, peri- 
carditis, etc., the excretion of uric acid appears to be quite con- 
stantly increased. 

Very interesting and suggestive are the data obtained in cases of 
true leukaemia, in which a daily excretion of from 1 to 5 grammes 
is frequently observed. The relation existing between the elimina- 
tion of uric acid and of urea may here vary from 1 : 45 to 1 : 19, 
or even 1 : 12. In a few cases of pseudo-leukaemia a like increase 
has been noted. In one case which the author had occasion to 
study for about three weeks the actual amount eliminated varied 
between 0.256 and 0.957 gramme, while the relation between it and 
urea varied from 1 : 64 to 1 : 22. In general it may said that the 
elimination of uric acid is increased in all splenic diseases. In per- 
nicious ana?mia the uric acid was found to be normal or increased. 
In dyspeptic disturbances the uric acid is frequently increased. In 
hepatic cirrhosis the relation of uric acid to urea has been found to 
vary from 1 : 19 to 1 : 33, while the amount of the former varied 
between 0.5 and 2 grammes. 

An increased elimination of uric acid, forming a disease sui gen- 
eris, as it were, must also be noted, constituting the so-called uric- 
arid diathesis, in which an enormous increase in the elimination of 
this substance appears to constitute the only objective symptom. 
Patients thus afflicted are the subjects of profound hypochondriasis 
and lose flesh rapidly. 

Da Costa has recently described a condition which is character- 
ized by the existence of certain nervous symptoms, such as listless- 
ness, fatigue upon slight exertion, headache, despondency, giddiness, 
and sleeplessness, associated with the elimination of a trace of albu- 
min and of large amounts of uric acid, oxalic acid, or of both. Car- 
diac hypertrophy and other cardiac lesions of Bright' s disease were 
conspicuously absent. The specific gravity in such cases is always 
high, varying between 1.022 and 1.036. The quantity of urine is 
about normal. The author has noted a considerable increase in the 
amount of urea in such cases. 

The excretion of uric acid in gout has been the subject of numerous 
investigations, aud while the causes producing the variations here 
observed are still a matter of great uncertain ity, a diminished 



352 CLINICAL DIAGNOSIS. 

elimination in the chronic state of the disease, especially marked 
immediately preceding the occurrence of exacerbations, as well as 
an increased elimination daring and immediately after an attack, 
may be regarded as indisputable facts. A resorption of the uric 
acid deposited in the form of tophi, in consequence of an increased 
degree of alkalinity of the blood, has been urged as the cause of 
acute attacks, the headaches and mental depression observed at 
these times being explained by the sudden flooding of the system, 
as it were, with uric acid. Whether or not we are dealing with a 
process of increased production or of diminished elimination of this 
substance in gout remains as yet to be decided. 

In diabetes a diminished amount of uric acid is usually found. 
Cases may be seen, however, in which, associated with a diminution 
in or an entire absence of sugar, there occurs a most marked in- 
crease in the amount of uric acid, amounting in some cases to 3 
grammes pro die. To this condition the term diabetes alternans has 
been applied. 

In the ordinary forms of anaemia and chlorosis the amount of uric 
acid is quite constantly diminished. So also in chronic interstitial 
nephritis, chronic lead-poisoning, progressive muscular atrophy, and 
pseudo-hypertrophic paralysis. 

Very interesting and suggestive is the increased elimination 
observed in acute articular rheumatism, returning to normal or 
even becoming subnormal with approaching convalescence. 

Fats and cane-sugar cause an increased elimination of uric acid. 
With a vegetable diet much less is excreted than with an animal 
diet. In a case cited by Bunge, 0.253 gramme was thus noted with 
the former diet, as compared with 1.398 grammes with the latter. 

It is, consequently, necessary to order for a patient the subject of 
the so-called uric-acid diathesis a diet containing as small an amount 
of nitrogenous material, particularly of animal origin, as possible. 
Foods rich in alkaline salts are indicated, such as potatoes, the 
more acid fruits, and berries. Cheeses should be avoided, being 
rich in albumins and very poor in alkaline salts. The reverse, of 
course, holds good when for any reason an increased elimination 
of uric acid appears advisable, the main factor to be considered in 
each case being the degree of alkalinity of the blood. Recently it 
has been shown that enormous amounts of uric acid are excreted 
under a diet rich in nucleins, thymus having been employed in the 
cases observed. 



THE URINE. 353 

Of drugs, salicylic acid and its salts, as well as disodium phos- 
phate, increase the elimination of uric acid. Alkalies, on the other 
hand, arc indicated when an excessive excretion exists, and the 
same may be said of potassium iodide, quinine, antipyrin, thallin, 
etc. 

Steam baths cause a most decided increase, amounting in some 
cases to twice or thrice the normal amount, the increase often 
persisting for several days. 

Properties of Uric Acid. Chemically uric acid is closely 
related to urea on the one hand, and to the xanthin-bases on the 
other. Its relation to urea is quite clear, if it be remembered that 
oxidizing agents transform uric acid into urea or into snbstituted 
ureas, such as allantoin and alloxan, which latter is closely related 
to parabanic acid, or oxalyl urea, and barbituric acid, or malonyl 
urea. 

The relation existing between these various substances is seen in 
the following equations, and it will be observed that uric acid, like 
the xanthin-bases, contains an alloxan and a urea radicle. Uric 
a«id plus xanthin-bases are hence also spoken of as alloxur bodies, 
and the relation existing between the elimination of uric acid- 
nitrogen and the alloxur bases-nitrogen has recently attracted 
much attention: 

1. C 5 H 4 N 4 3 -f H 2 + O = C 4 H 6 N 4 + C0 2 
Uric acid. Allantoin. 

2. C 5 H 4 N 4 O a + H 2 + O = C 4 H 2 N 2 4 + CON 2 H 4 

Uric acid. Alloxan. Urea. 

3. C 4 H a N 2 4 + O = C 3 H 2 N 2 3 + C0 2 

Alloxan. Parabanic acid. 

The relation existing between uric acid and the xanthin-bases is 
seen from the following formulae: 

Ilypoxanthin C 5 H 4 N 4 

Xanthin C 5 H 4 N 4 2 

Uric acid C 5 H 4 N 4 3 

Guanin C 5 H 5 N 3 

As a matter of fact, it is possible to produce xanthin and hypo- 
xanthin from uric acid by a process of reduction. 

Uric acid forms a white, crystalline powder which is almost in- 
soluble in cold water (1 : 14,000), difficultly soluble in boiling water 
(1 : 1800), and insoluble in alcohol and ether. In concentrated 
sulphuric acid it readily dissolves, but is precipitated upon dilution 

23 



35-4 



CLIXICAL DIAGXOSIS. 



with water. Id aqueous solutions of the alkaline carbonates and 
hydrates it dissolves with the formation of acid — viz.. neutral — 
salts, as represented in the following equations: 

C 5 H<X 4 3 — Xa,C0 3 = C 5 H 3 N a N 4 : — NaEKXX 
CJBJS& - 2Na OH = C^Na^A - H 2 0. 

In the urine the amount of water present would not be sufficient 
to hold the uric acid in solution, this being accomplished by the 
disodium phosphate, as pointed out above. 

Uric acid is found in the urine in the form of sodium, potassium, 
and ammonium salts, traces of ealeiuni and magnesium compounds 
being possibly also present. These salts may be decomposed by 
the addition of a sufficiently large quantity of a stronger acid, 
such as hydrochloric acid, when uric acid is set free: 
C 5 H : >^_\\<J: - 2HC1 = C 5 H 4 X 4 3 - 2NaCL 

If, on the other hand, the amount of acid added be insufficient, 
the acid salt is thrown down: 

•: f H ; >~2 : >~ 4 3 - HCl = CILXa^A - Nad 

All these salts are difficultly soluble, and are, hence, precipitated 
whenever the urine is markedly acid or concentrated, and also when 



7::- 9S 




1 >r J 



Various forms of uric-acid crystals. Fenlayson. 



it is exposed to a low temperature. This holds good particularly 
for the acid salts, notably the ammonium compound. 

Uric acid that has separated out from the urine spontaneously 
may occur under a great variety of forms Fig. 89), of which the 



THE URINE, 355 

ailed whetstone-form is the most characteristic (see Sediments). 
When obtained from its alkaline solutions by the addition of hydro- 
ehloric acid it usually forms small rhombie plates, which taper 
markedly toward their ends, being often club-shaped. 

Of the compounds which uric acid forms with the heavy metals, 
the silver salt is especially important. When a solution of uric 
aeid in ammonia is treated with an ammoniacal solution of silver 
nitrate the solution remains clear. If, then, calcium chloride, 
sodium chloride, or magnesia mixture be added, a precipitate is 
formed which contains the uric acid in combination with the silver. 

Tests for Uric Acid. About 200 c.c. of filtered urine are 
treated with 10 c.c. of hydrochloric acid and set aside in a cool 
place for twenty-four to forty-eight hours. The uric acid which 
has separated out is then collected on a filter and subjected to fur- 
ther tests: 

1. Mwrexid lest. A few crystals are dissloved by means of a few 
drops of concentrated nitric acid, with the application of heat, upon 
a porcelain plate, such as the cover of a crucible. The nitric acid is 
then carefully evaporated, when a yellowish-red spot will be found 
to remain. Upon cooling a drop of ammonia is placed upon this 
spot, when in the presence of uric acid a beautiful purplish-red 
color will develop, owing to the formation of ammonium purpurate 
(murexid). If now a drop of sodium hydrate solution be added, 
the color will change to a reddish-blue, which disappears upon 
heating, thus differing from the somewhat similar xanthin reaction. 

2. ( 'ojjper test. A few crystals are dissolved in sodium-hydrate 
solution and treated with a few drops of Fehling's solution. Upon 
the application of heat white urate of copper separates out, while 
red cuprous oxide appears if a relatively large amount of copper 
sulphate be present, a point to be remembered in testing for sugar. 

.*}. AVhen treated with sodium hypobromite solution uric acid gives 
up about 47 per cent, of its nitrogen. 

Quantitative Estimation of Uric Acid. 

Hopkin-' Method. This method is destined soon to replace 
the more complicated procedures which have hitherto been em- 
ployed in the clinical laboratory (see below), as it is much simpler 
and at the same time just as accurate as the older method of Ludwig- 
Salkowski and that of Haycraft. 

Principle: The method is based upon the observation that ammo- 



356 CLINICAL DIAGNOSIS. 

niam biurate is altogether insoluble in solutions of ammonium 
chloride. If, then, a specimen of urine be saturated with ammo- 
nium chloride, the various urates are transformed into ammonium 
biurate and precipitated as such. The salt is then decomposed 
with hydrochloric acid and the uric acid estimated, either gravi- 
metrically or vol u metrically, as described below. 

Method: 100 c.c. of urine are treated with 30 grammes of finely 
powdered and chemically pure ammonium chloride. The mixture 
is thoroughly shaken and set aside for from two to three hours, 
care being taken to stir it from time to time. It is then passed 
through a small filter and the precipitate washed two or three 
times with a saturated solution of ammonium chloride. With the 
aid of a little boiling water the salt is washed from the filter and 
decomposed by the addition of 5 c.c. of a 25 per cent, solution of 
hydrochloric acid. This solution is evaporated until crystals of 
uric acid begin to separate out. These may then be collected on a 
dried and weighed filter and washed successively with water, 90 to 
94 per cent, alcohol, absolute alcohol, and finally with ether. The 
water used in washing should be collected separately and 0.0048 
gramme added to the weight of uric acid obtained for every 10 
c.c. used. 

More convenient, according to the writer's experience, and just 
as accurate, is the volumetric estimation of the uric acid as sug- 
gested by Hopkins. To this end the uric acid is collected on a 
glass-wool or asbestos filter and treated as described above. The 
precipitate, together with the glass-wool or asbestos, is then placed 
in a beaker and the uric acid dissolved in as small an amount of a 
30 per cent, solution of sodium carbonate as possible with the aid 
of heat. Upon cooling this solution is diluted with water to 100 
c. c. , treated with 20 c. c. of concentrated sulphuric acid, and titrated, 
while warm, with a one-twentieth normal solution of potassium 
permanganate until the rose-red color which at first appears upon 
the addition of each drop no longer disappears on stirring. As 1 
c.c. of the permanganate solution corresponds to 3.61 milligrammes 
of uric acid, the amount of the latter contained in 100 c.c. of urine 
is found by multiplying the number of c.c. used with 3.61. 

Haycraft's Method. This method is based upon the precipi- 
tation of uric acid with an ammoniacal silver solution and magnesia 
mixture, 1 molecule of silver corresponding to 1 molecule of uric 
acid. As the amount of silver thus precipitated can be determined 



THE URINE. 357 

by titration with a solution of potassium sulpho-cyanide, the corre- 
sponding amount of uric acid is readily found. 

Solutions required: 1. An ammoniacal silver solution. 2. An 
ammoniacal magnesia mixture. 3. A one-fiftieth normal solution 
of nitrate of silver. 4. A one-fiftieth normal solution of potassium 
sulpho-cyanide. 

Preparation of these solutions: 

1. The ammoniacal silver solution is prepared by dissolving 26 
grammes of nitrate of silver in distilled water, adding enough 
ammonia to redissolve the brown precipitate of oxide of silver first 
formed; distilled water is then added in sufficient amount to make 
the total quantity 950 c.c. This solution is brought to its proper 
strength by titrating a known amount of sodium chloride as de- 
scribed elsewhere. Each c.c. then contains 0.026 gramme of nitrate 
of silver, equivalent to 0.00216 gramme of silver. 

2. The ammoniacal magnesia mixture is prepared by dissolving 
100 grammes of crystallized magnesium chloride in a sufficient 
amount of water, to which a cold saturated solution of ammonium 
chloride is added in excess, and enough strong ammonia to impart 
a decided odor. Should the mixture not be perfectly clear, still 
more ammonium chloride solution is added. The solution is then 
diluted with water to 1 liter. 

3. The one-fiftieth normal solution of nitrate of silver is prepared 
by dissolving 3.4 grammes of silver nitrate in 950 c.c. of distilled 
water, the degree of further dilution being determined as described 
elsewhere. 

4. To prepare the one-fiftieth normal solution of potassium sulpho- 
cyanide, about 2 grammes of the salt are dissolved in 950 c.c. of 
water and the solution brought to the required strength, so that 1 
c.c. shall correspond to 1 c.c. of the silver solution. 

For filtering the uric acid a perforated platinum cone is placed in 
a small funnel and packed with a fine layer of glass-wool, upon 
which in turn a layer of finely scraped asbestos is placed, this 
having been thoroughly washed out in very dilute hydrochloric 
acid and subsequently with distilled water until every trace of 
chlorine has disappeared, the asbestos forming, as it were, a mould 
of the cone. 

Method: Five c.c. of the ammoniacal silver solution are mixed 
with 5 c.c. of the ammoniacal magnesia mixture. Ammonia is 
then added until the solution is clear, when it is poured into 



358 CLINICAL DIAGNOSIS. 

50 c.c. of urine. As soon as the precipitate has settled the super- 
natant liquid is filtered through the filter prepared as described, 
with the aid of a suction-pump. About 4 grammes of sodium 
bicarbonate in coarse pieces are now placed upon the filter and 
the precipitate added, the sodium bicarbonate serving the pur- 
pose of aiding filtration by loosening the precipitate. This is now 
washed free from chlorine and silver by means of ammoniacal 
water, using the suction-pump, until the precipitate appears broken 
in places, then without the pump, using this only at last to remove 
the last drops of liquid. Test for silver with very dilute hydro- 
chloric acid, and for chlorine with a solution of nitrate of silver 
and nitric acid. The precipitate thus obtained is dissolved on the 
filter by means of 20 to 30 per cent, nitric acid. The nitric acid 
must be free from nitrous acid. This is accomplished by allowing 
it to stand in contact with pure urea until all evolution of gas has 
ceased. The filter is washed with very dilute nitric acid and then 
with distilled water, until this no longer shows an acid reaction. 
The solution thus obtained is titrated with the one-fiftieth solution 
of potassium sulpho-cyanide, using am monio-f erric alum as an in- 
dicator. As every c.c. of this solution indicates 0.00216 gramme 
of silver, and as 1 molecule of silver indicates 1 molecule of uric 
acid — i. e., 108 grammes of silver 168 grammes of uric acid — 
0.00216 gramme of silver, corresponding to 1 c.c. of the potassium 
sulpho-cyanide solution, represents 0.00336 gramme of uric acid. 

Ludwig-Salkowski Method. This method should be em- 
ployed whenever special accuracy is required. 

Principle: A solution of uric acid in sodium carbonate when 
treated with a solution of nitrate of silver, after a previous addition 
of an excess of ammonia, gives rise to a flaky, gelatinous precipitate 
containing uric acid, sodium, and silver, which is very difficultly 
soluble. From this the silver may be removed, and the compound 
of uric acid and sodium decomposed by means of hydrochloric 
acid. 

Method: Two hundred and fifty c.c. of urine are treated with 50 
c.c. of ammoniacal magnesia mixture (see above) for the purpose 
of removing the phosphates. The magnesia mixture is employed 
for the reason that the compound of uric acid with magnesium and 
silver formed later on is not decomposed as easily as the sodium or 
the potassium compound, which would occur if the urine were only 
precipitated with ammonia. The mixture is then immediately 



THE URINE. 359 

filtered, as otherwise a little magnesium urate would be precipitated; 
2-~)<) c.c. of the liltrate, corresponding to 200 c.c. of urine, are meas- 
ured off as soon as possible and treated with a few c.c. of a 3 per 
cent, solution of nitrate of silver. If the precipitated silver chlo- 
ride formed in the beginning does not disappear on stirring, a little 
more ammonium hydrate is added. A flaky precipitate falls next, 
which is allowed to settle. In order to test whether enough of the 
silver nitrate solution has been added, a few c.c. of the supernatant 
fluid are acidified with nitric acid. If a distinct cloudiness appears, 
referable to silver chloride, enough has been added. Otherwise the 
few c.c. that were employed for this test are rendered alkaline again 
with ammonia, poured back, and more silver solution added until 
the required amount has been reached. The liquid is then rapidly 
filtered through a folded filter of rather loose paper, a feather or 
rubber-tipped glass rod being used for the purpose of removing all 
the precipitate from the beaker. The precipitate is washed until a 
specimen of the washings is no longer rendered turbid by nitric 
acid, and only faintly so by the addition of a drop of silver solu- 
tion. The filter w T ith the precipitate is next placed in a wide- 
mouthed flask containing about 200 c.c. of distilled water, and the 
mixture thoroughly shaken. Sulphuretted hydrogen is then passed 
tli rough the mixture, which is thoroughly shaken from time to 
time. It is then brought to the boiling-point and rendered dis- 
tinctly acid by meaus of a few drops of hydrochloric acid, when 
the sulphide of silver and the paper are rapidly filtered off, as 
otherwise there will be an admixture of sulphur to the uric 
acid. The contents of the filter are washed a few times with hot 
water. Filtrate and washings are quickly evaporated to a few 
c.c, to which a few drops of hydrochloric acid are added, and then 
- t aside in a cool place for twenty-four hours. Occasionally it 
happens that upon the addition of the hydrochloric acid a cloudi- 
ness appears, due to an admixture of sulphur. In such a case the 
dried uric acid must be washed with carbon disulphide. Other- 
wise the uric acid that has separated out is directly collected on a 
dried and weighed filter and washed successively with water, 90 to 
94 per cent, alcohol, and finally with absolute alcohol and ether. 
The water used in washing should be collected separately, and 
0.0048 gramme added to the weight of the uric acid obtained for 
every 10 c.c. used. 

Precautions : 1. Rapidity in working is most essential. 



360 CLINICAL DIAGNOSIS. 

2. Very concentrated urines must be diluted one-half before 
commencing the test. 

3. If the specific gravity of the urine be low, it should be con- 
centrated to a specific gravity of about 1.020. 

4. If the urine show a sediment of uric acid, this should be 
separately collected and weighed, and the weight obtained added to 
the final result. 

5. Any albumin present should be previously removed. 

6. If sugar be present in the urine, about 500 to 1000 c.c. are 
treated with a solution of neutral acetate of lead, filtered, and the 
filtrate precipitated with mercuric acetate. The precipitate thus 
formed, which consists essentially of mercuric urate, is filtered off 
after having stood for twelve to twenty-four hours, first washed 
with and later suspended in water. The mercury is removed by 
means of sulphuretted hydrogen, the suphide of mercury filtered 
off, and the filtrate collected and set aside. The precipitate itself 
is thoroughly boiled with water and again filtered, the washings 
thus obtained being added to the filtrate set aside, as just described. 
The total amount of fluid is then evaporated to a small volume and 
acidified with hydrochloric acid, when the uric acid will separate 
out and may be treated as previously directed. 

The Old Method of Heixtz. The following method, although 
inaccurate, may be employed when the necessary solutions required 
for more accurate working are not at hand: 

Principle: The urates contained in the urine are decomposed by 
means of hydrochloric acid, the uric acid formed being set free. 

Fig. 90. 




Watch-crystals. (W. Simon 



Method: Two hundred c.c. of urine are treated with 10 c.c. of 
strong hydrochloric acid and set aside in a cool place for forty- 
eight hours. The crystals of uric acid which have been deposited 
by that time are collected on a small filter that has been dried at a 
temperature of 110° to 115° C, and carefully weighed, using a cut- 
feather or a rubber-tipped glass rod to remove all the crystals from 



THE URINE. 361 

the bottom and sides of the vessel, portions of the filtrate being 
used to bring the last traces upon the filter. The crystals are then 
washed with eold water, care being taken to collect the washings 
separately, until a speeimen no longer becomes cloudy when treated 
with a few drops of nitrate of silver and nitrie acid. Funnel and 
filter arc then dried in the hot-air bath at a temperature of 110° to 
1 1 5° C, and the filter finally dried to a constant weight at the same 
temperature. The filter is most conveniently dried between watch- 
i:ia<scs (Fig. 0<>), two of these being employed, one placed inside 
the other during the process of drying, while one is covered by the 
other and held in position by a spring during the process of weigh- 
ing. The weight of the glasses and clamp, as well as that of the 
filter, is deducted from the total weight, the difference indicating 
the weight of the uric acid contained in 200 c.c. of urine. As the 
uric acid, how r ever, is slightly soluble iu acidified urine and acidi- 
fied water, a loss will always arise if this method be employed. If 
bat 30 c.c. of water are used during the process of washing, how- 
ever, the loss will practically be counterbalanced by the weight of 
the coloring -matter which is carried down by the crystals. It has 
been estimated, furthermore, that for every 10 c.c. of water used 
beyond the amount indicated the addition of 0.0045 gramme to the 
weight obtaiued will make up for the loss of uric acid thus resulting. 

While this method may be employed for clinical purposes, 
it must be remembered that at times only a portion of the uric 
acid, or none at all, separates out. Its absence should not, how- 
ever, be inferred under such conditions, as its presence may be 
demonstrated by alkalinizing the acid filtrate and treating this 
with a solution of nitrate of silver, when a considerable precipita- 
tion may occur, referable to the presence of uric acid. A test such 
a- this should always be made, and if a considerable cloudiness be 
obtained, recourse should be had to one of the methods indicated 
above. 

In addition to the precautions given the following should be 
noted: 

Urines rich in uric acid should be warmed after the addition 
of the hydrochloric acid until the cloudiness which occurs upon the 
addition of the reagent owing to the presence of acid urates has dis- 
appeared. If a sediment or cloudiness, due to urates, be noted in 
the urine, it should be warmed, and if necessary a small amount of 
alkali added, before the addition of the hydrochloric acid. 



362 CLINICAL DIAGNOSIS. 

Hippuric Acid. 

Hippuric acid is a constant constituent of normal urine, 0.1 to 1 
gramme being excreted in the twenty-four hours. That it is derived 
to some extent at least from albuminous material is proved by the 
fact that its elimination is not suspended during starvation or dur- 
ing the administration of a purely albuminous diet. The manner 
in which hippuric acid is formed in the body-economy, however, 
has not been definitely ascertained. ' In vitro it may be obtained 
from glycocoll and benzoic acid, according to the equation: 

C 6 H 5 — CH.,>""H„ = CH.NH — C 6 H 5 CO — H„0 

III 

COOH COOH COOH 

Benzoic acid. Glycocoll. Hippuric acid. 

It has been shown that phenyl-propionic acid, which differs from 
benzoic acid by the group C 2 H 4 , and which latter may be regarded 
as phenyl-formic acid, is produced during the process of intestinal 
putrefaction, the relation between the two bodies being seen from 
the formula?: 



H C 6 H 5 
COOH" " COOH 


CH 3 CH 2 C 6 H 5 

1 ! 
CH 2 ■ ^ CH 2 

COOH COOH 


Formic Phenyl-formic 
acid. acid. 


Propionic Phenyl-propionic 
acid. acid. 



Phenyl-propionic acid is then absorbed into the blood and there, 
according to our present ideas, transformed into phenyl-formic acid, 
or benzoic acid. The latter coming into contact with glycocoll, 
which is probably produced during the process of intestinal putre- 
faction also, an interaction between the two substances occurs, hip- 
puric acid resulting, as shown in the above equation. This view is 
supported by the fact that phenyl-propionic acid, just as benzoic 
acid, when introduced into the circulation of certain animals, reap- 
pears in the urine as hippuric acid. The final proof of the possible 
synthesis of hippuric acid from glycocoll and benzoic acid in the 
body has been furnished by Bunge and Schmiedeberg, who obtained 
this substance when arterialized blood containing glycocoll and 
sodium benzoate was allowed to pass through isolated kidneys of 
dogs. 

Not all the hippuric acid eliminated, however, is referable to 
albuminous material, but a considerable portion is derived from 
benzoic acid, or its derivatives, which latter, contained in many of 



THE URINE. 363 

the fruits eaten as food, are transformed into hippuric aeid in the 
body. Among those which are particularly rich in these substances 
there must be mentioned the red bilberry, prunes, coffee-beans, 
reines-elaudes, etc., and in all cases in which an increased elimina- 
tion of hippuric aeid is observed the possibility of this source 
must always be taken into account. 

As to the seat of this synthesis there appears to be some uncer- 
tainty, it not appearing to be the same in all animals. In the dog 
and the frog the kidneys, according to the researches of Bunge and 
Schmiedeberg, must be regarded as the principal and possibly the 
only organs in which this process occurs. As Salomon, however, 
has demonstrated the presence of hippuric acid in the muscles, liver, 
and blood of nephrectomized rabbits, there must be, in the herbivora 
at least, other organs concerned in its production. 

Very little is known of the pathologic variations in the excretion 
of hippuric acid, principally owing to the fact that suitable methods 
for its quantitative estimation were unknown until recently. It is 
an interesting fact that, in accordance with Bunge' s experiments 
in dogs, the elimination of hippuric acid appears to be entirely 
suspended in cases of acute as well as chronic parenchymatous 
nephritis following the ingestion of benzoic acid, this reappearing 
unchanged in the urine. In amyloid degeneration a marked dimi- 
nution in its amount has likewise been demonstrated. Large quan- 
tities of hippuric acid, on the other hand, have been noted in acute 
febrile diseases, hepatic diseases, diabetes mellitus, chorea, etc. The 
data, however, are insufficient to warrant any definite conclusions 
at the present time. 

Properties of Hippuric Acid. Chemically, hippuric acid must 
be regarded as benzoyl-amido-acetic acid, C 9 H 9 X0 3 (C 6 H 5 .CONH. 
CHoCOOH). It crystallizes in long rhombic prisms when allowed 
to separate from its solutions gradually, while it forms long needles 
if crystallization takes place rapidly and the amount is small (Fig. 
91). In water and ether it is soluble with difficulty, while it dis- 
solves readily in alcohol and in aqueous solutions of the hydrates 
and carbonates of the alkalies, forming salts, from which the acid 
may again be separated and caused to crystallize out upon the addi- 
tion of a stronger acid. 

When hippuric acid or one of its salts is evaporated to dryness 
with concentrated nitric acid aud the residue heated, the odor of 
bitter almonds is noticed, due to the formation of nitro-benzol. 



364 



CLIXICAL DIAGXOSIS. 



When boiled with hydrochloric acid or dilute sulphuric acid it 
is decomposed into glycocoll and benzoic acid. A similar decom- 
position is effected during the process of putrefaction, and hence no 

hipparic acid is found in decomposing urine. : izolc acid taking its 
place. The latter is always found in the urine together with hip- 
paric acid, but has no clinical significance. In large amounts it 
has recently been found in a case of diabetes. It crystallizes in 
lustrous lamina? or needles, the former presenting ra^ed ed^es and 



J:--. :-:. 




Hippuric-acid crystals. 

resembling somewhat plates of cholesterin. It is difficultly soluble 
in cold water, but easily soluble in ether, alcohol, and solution- :: 
the alkaline carbonates and hydrates, forming salts with the latter. 

Hippuric acid in the urine occurs in combination with sodium. 
potassium, calcium, and magnesium. 

Quantitative Estimation of Hippuric Acid. The following 
method, which may be employed for the quantitative estimation of 
hippuric acid, although very tedious, must also be employed when 
it is desired to test for its presence. 

Principle: Hippuric acid readily dissolves in solution- of the 
alkaline hydrates and carbonates, forming salts. These are deeoni- 

sed by meaus of a stronger acid, when the hippuric acid which 
separates out is collected and weighed. 

Method: Five hundred to one thousand c.c. of fresh urine are 
evaporated to a syrupy consistence on a water-bath, care being taken 
to keep the urine neutral by the addition of sodium carbonate. 
The residue is extracted with cold alcohol ~ per cent. . 



THE URINE. 365 

taking about half of the quantity as that of urine employed, 
and setting aside the mixture for twenty-four hours. The alco- 
holic filtrate, which contains the salts of hippuric acid, is then 
freed from alcohol by distillation. The remaining solution is 
strongly aeidilied with acetic acid, in order to liberate the lactic 
aeid, and extracted with at least five times its own volume of alco- 
holic ether (1 part of alcohol to 9 parts of ether). From the com- 
bined extracts the ether is distilled off and the remaining solution 
evaporated on a water-bath. The resinous residue is boiled Avith 
water, set aside to cool, and filtered through a well-moistened filter. 
The hippuric acid, which is easily soluble in boiling water, is thus 
separated from other constituents soluble in alcohol and ether. The 
filtrate is rendered alkaline with a little milk of lime, any excess of 
calcium hydrate being removed by passing carbon dioxide through 
the mixture. This is then brought to the boiling-point and filtered. 
Any impurities present are removed by shaking with ether. The 
calcium salts remaining in solution are decomposed by means of an 
acid and the solution again extracted with ether. The remaining 
solution is evaporated to a few c.c, when the hippuric acid will 
separate out on standing. The crystals are dried on plates of plaster- 
of-Paris, shaken with benzol or petroleum-ether to remove any ben- 
zoic acid, and finally weighed. These crystals may be shown to be 
hippuric acid by their microscopic appearance, their solubility in 
alcohol, and their behavior when evaporated with concentrated 
nitric acid as indicated above. 

Hofmetster's Method. Two hundred to three hundred c.c. of 
urine are evaporated in a glass dish to one-third of the original volume, 
treated with 4 grammes of disodium phosphate to transform the acid 
into its sodium salt, and the mixture evaporated to a syrupy con- 
sistence. The residue is treated with burnt gypsum, dried thor- 
oughly, and pulverized together with the dish. The powder is 
extracted in a Soxhlet apparatus with freshly rectified petroleum- 
ether (boiling-point 60° to 80° C.) for forty-six hours, and then for 
six to ten hours with pure ether (free from water and alcohol). 
After distilling off the ether, the residue is dissolved in boiling water 
and decolorized with animal charcoal, the latter being subsequently 
thoroughly washed with boiling water; the solution and washings 
are evaporated to about 1 or 2 c.c. at a temperature of from 50° to 
6( >° C. , and set aside to crystallize. The crystals of hippuric acid are 
finally washed with a few drops of water and ether, and weighed. 



366 CLINICAL DIAGNOSIS. 



Kreatin and Kreatinin. 



Numerous observatioas point to kreatin, which is constantly 
present in muscle-tissue, as being in all probability the immediate 
and constant antecedent of kreatinin, so that two sources of this 
body must be recognized, viz., the muscle-tissue of the body and 
the muscle-tissue ingested as food. Beyond this, however, practi- 
cally nothing is known, and as the artificial production of kreatinin 
from albuminous material has so far never been accomplished, it is 
hardly warrantable to venture an hypothesis as to its mode of for- 
mation in the body. 

Kreatinin is a constant constituent of the urine, about 1 gramme 
being daily excreted by a healthy adult. Pathologically variations 
in this amount have been observed, but the data so far obtained 
possess little value, and before drawing any conclusions from facts 
chemically observed it is necessary to take into account the quantity 
of meat ingested by the individual, as a meat-diet will increase the 
amount of kreatinin, while this will be diminished by a milk-diet. 
If then in patients affected with acute febrile diseases, such as pneu- 
monia, typhoid fever, etc., a large increase is observed, the patient 
being at the same time upon a milk-diet, an increased destruction 
of muscle-tissue may be inferred. A decrease would logically be 
expected to occur during convalescence from such diseases. In the 
various forms of anaemia, marasmus, chlorosis, phthisis, etc., a 
diminished amount is observed. 

The transformation of kreatin into kreatinin has been supposed 
to take place in the kidneys, a view which accords with the greatly 
diminished excretion of kreatinin in well-advanced cases of chronic 
parenchymatous nephritis. In progressive muscular atrophy, in 
pseudo-hypertrophic paralysis, and in progressive ossifying myositis 
a diminution has been noted. 

Properties of Kreatin and Kreatinin. Chemically kreatin 
may be regarded as a methyl derivative of glycocyanin, which 
latter is guanidin in which one NH 2 group has been replaced by 
glycocoll. Kreatinin, on the other hand, is the methyl derivative 
of glycocyanidin, which differs from glycocyanin only in the absence 
of 1 molecule of water, so that kreatinin is kreatin minus 1 molecule 
of water, both being derivatives of guanidin. The relation between 
the various bodies is as follows: 



i 



THE 


URINE. 


/NH 3 
C=NH 

\nh 8 




Guanidin. 




/NIL 
C=N 1 1 
\MI.( IL.COOH 
Glycocyanin. 


/NH 2 

C=MI 
\N(CH 3 ).CH 2 .COOH 

Kreatin. 


7 NH 
C=NH 
\NH.CH a .CO 

Glycocyanidin (glycocyanin minus water). 


C-N 

\N(CH 3 ).CH 2 .CO 
Kreatinin (kreatin minus water) 



367 



Kreatinin crystallizes without water of crystallization in colorless, 
glistening prisms. At times, when the crystals are not well devel- 
oped, it also appears in the form of whetstones. It is readily 
soluble in hot and also quite soluble in cold water and hot alcohol, 
but more difficultly so in cold alcohol and ether. 

It forms salts with acids and double salts with some of the salts 
of the heavy metals. Among these may be mentioned kreatinin 
hydrochloride, C 4 H 7 N 3 0.HC1, which is easily soluble in water and 
crystallizes in the form of transparent prisms or rhombic plates. 
Most important is the compound of kreatinin with zinc chloride 



Fig. 92 




Crystals of kreatinin-zinc chloride. (Salkowski.) 

(CH 7 X 3 0) 2 .ZiiC1 2 (Fig. 92). This is produced when a watery or 
alcoholic solution of kreatinin is treated with chloride of zinc. The 
crystalline form of this compound depends greatly upon the purity 
of the kreatinin solution. When obtained from alcoholic extracts 
of the urine it occurs in the form of varicose conglomerations which 
often adhere firmly to the walls of the vessel. If the solution of 



368 CLINICAL DIAGNOSIS. 

kreatiniu be perfectly pure, however, it is seen in the form of fine 
needles grouped together in rosettes or sheaves. Kreatinin-zinc 
chloride is very difficultly soluble in water and insoluble in alcohol. 
This compound is especially important, as upon its formation and 
properties the quantitative estimation of kreatinin in the urine is 
based. Nitrate of silver and mercuric chloride cause a precipita- 
tion of kreatinin. and may. therefore, also be employed for the pur- 
pose of obtaining the substance from the urine. 

Test for Kreatinin in the Urine. A few c.c. of urine are 
treated with a few drops of a very dilute solution of sodium nitro- 
prusside, and then drop by drop with a dilute solution of sodium 
hydrate, when the urine in the presence of kreatinin assumes 
a ruby-red color, which is particularly well seen in the lowest 
portion of the tube. This color disappears after a few minutes, 
and is replaced by an intensely yellow color, which, on warming 
with glacial acetic acid in pure solutions, gives rise to a green color 
WeyPs ted). The presence of albumin or sugar does not interfere 
with the reaction. 

Quantitative Estimation of Kreatinin in the Urine. Prin- 
ciple: TThen an alcoholic extract of the urine is treated with an 
alcoholic solution of zinc chloride, kreatinin-zinc chloride separates 
out, which, as has been mentioned, is almost insoluble in alcohol. 
Knowing the molecular weight of kreatinin and kreatinin-zinc chlo- 
ride, the calculation of the amount of kreatinin becomes a simple 
matter. The molecular weight of kreatinin is 113. that of krea- 
tinin-zinc chloride 362. In 362 parts by weight of the latter there 
are, hence, 226 parts by weight of the former, so that the amount 
of the kreatinin may be calculated from the weight of kreatinin- 
zinc chloride according to the following equation: 362 : 226 : : y : x, 
and x = 0.6243y, in which y indicates the weight of the kreatinin- 
zin: chloride found, and x the corresponding amount of kreatinin. 
The phosphates must, of course, first be eliminated, as insoluble 
zinc phosphate would otherwise be precipitated. 

Method: In 240 c.c. of urine the phosphates are first removed 
by rendering the urine alkaline with milk of lime and then addiug 
calcium chloride as long as a precipitate forms. If the volume now 
be less than 300 c.c, water is added to that amount. The mixture 
is filtered after having been allowed to stand for one-qaurter to one- 
half hour, and washed with a little water; 250 c.c. of the mix- 
ture are then measured off, slightly acidified with dilute hydrochloric 



THE URINE. 369 

acid so as to prevent any transformation of kreatinin into kreatin 
during the long process of evaporation. This amount is evaporated 
on a water-bath to a syrupy consistence, and then thoroughly mixed 
with 20 to 30 c.e. of absolute alcohol. The mixture is poured into 
a stoppered flask provided with a 100 c.c. mark, and after thor- 
oughly rinsing out the evaporating-dish with absolute alcohol the 
washings are also placed in the bottle and absolute alcohol added to 
the loo c.c. mark. The bottle is thoroughly shaken and set aside in 
a cool place for twenty-four hours, the mixture being agitated from 
time to time. It is now filtered and rendered slightly alkaline with 
a drop or two of sodium carbonate solution, as kreatinin hydrochlo- 
ride is not precipitated by chloride of zinc. The reaction, however, 
should be only faintly alkaline, as otherwise zinc oxide will be pre- 
cipitated. The mixture is now slightly acidified with acetic acid. 
Eighty c.c, corresponding to 160 c.c. of urine, are treated with 10 
to 15 drops of an alcoholic solution of zinc chloride, prepared by dis- 
solving the salt in 80 per cent, alcohol and diluting with 95 per cent, 
alcohol to a specific gravity of 1.2. The mixture is then well stirred 
and set aside in a cool place for two or three days. The crystals, 
which are usually deposited upon the sides of the vessel in the form 
of wart-like masses, are then collected upon a dried and weighed 
filter, always using portions of the filtrate to bring the crystals com- 
pletely upon the filter. These are washed with a small amount of 
!»< > per cent, alcohol until the washings are without color and give 
only a slight opalescence when treated with a drop of nitrate of 
silver solution. The crystals are finally dried at a temperature of 
loo C., and weighed. By multiplying the weight thus found by 
< UI2I3 the amount of kreatinin is obtained. 

Precautious: 1. Albumin and sugar, if present, must first be 
removed. In diabetic urines it is best, after having removed the 
sugar by fermentation, to take one-fifth of the total quantity elimi- 
nated in twenty-four hours, and to evaporate this to about 300 c.c. 
before removing the phosphates. 

2. The weighed material should be examined microscopically to see 
whether notable quantities of sodium chloride be present. Should 
such be the case it is necessary to determine the amount of zinc present 
and to estimate the kreatinin from this. To this end the alcoholic 
solution containing the kreatiuin-zinc chloride is evaporated to dry- 
ness after the addition of a little nitric acid. The residue is incin- 
erated, extracted with water, washed, dried, fused, and finally weighed. 

24 



37m '.iiyi'iAi z<:a -:\ \i>. 

As i parts ::' kreatinin-zinc chloride correspond to 22.4 parts 
"eight of zinc oxide, the corresponding amount of the compound 
is fcMind according to the following equation: 22.4 : 100 : : y : x, 
and x = 4. 4642, in which y represents the amount of zinc oxide 
found, and x the corresponding amount of kreatinin-zinc chloride. 
By multiplying the number thus ascertained by 0.6243 the corre- 
sponding amount of kreatinin is found. 

3. Instead of doing this the precipitate in the alcoholic solution 
may be examined microscopically before filtering, and if sodium 
chloride ~:als be found, providing that the kreatinin-zinc chlo- 
ride crystals adhere to the sides of the vessel, the sodium chloride 
may be dissolved in a little water and poured off, 

4. If the crystals of kreatinin-zinc chloride adhere very firmly 
to the sides : the vessel, so that their removal would be incomplete, 
it is perhaps best to dissolve them in a little hot water, to evaporate 
: Iryness, : ago the kreatinin compound direct _ 

5. If the urine shows an alkaline reaction, it is best to acidify j 
with sulphuric acid and to boil for half an hour before removing the 
phosphates, so as tc transform any kreatin that may be present into 
kreatinin. when the examination should be continued as described. 

riie Xanthin Bases. 

The xanthin bases which have been found in the orine are: xan- 
thin, heteroxanthin, paraxanthin, hypoxanthin, guanin, adenin, and 
carnin. The relation existing between these bodies is seen from 

their formula?: 

Hypoxanthin C 3 H 4 X 4 

Xanthin C^N/), 

Heteroxanthin C 5 H 3 (CH 3 ) X 4 2 

Paraxanthin CjH^CHj),^ 

Adenin C 5 H f y= 

Goanin C 5 H 5 X 5 

Carnin I > 4 3 

Like uric acid, they are undoubtedly derived from nuclein, am 
follows 

Albumin. 



X ::Le:r 



Xucleinic acid 



Phosphoric acid. 



Adenin. 
Guanin. 
Xanthin. 

Hypoxamhin. 



THE URINE, 371 

Individually the xanthin bases are of little interest. In splenic 
leukemia hypoxanthin is usually found in increased amount. Xan- 
thin, as such, has been found in urinary sediments, and a few cases 
arc on record where calculi were observed, consisting of almost the 
pure substance. The reactions by means of which xanthin may be 
recognized will be described in the chapter on Sediments. 

Conjointly, the xanthin bases are spoken of as alloxur bases, as 
they all contain an alloxan as well as a urea radicle, 



X— c 


— N 


V A 




\ 1 

N-C 


— N^ 


Alloxan 
radicle. 


Urea 
radicle 



joined together in a characteristic manner. 

Of late, the elimination of nitrogen in ihis form, as compared 
with the total amount of nitrogen and that excreted as uric acid, 
has occupied the attention of numerous investigators. The entire 
subject, however, is in a somewhat chaotic condition as yet, and the 
time has not arrived where it would be admissible to draw definite 
conclusions from the work accomplished. It must be admitted, 
moreover, that the method of Kriiger and Wulff, which has been 
almost exclusively employed in the estimation of the alloxur nitro- 
gen, is by no means free from objections. The values obtained are 
usually much higher thau those reached with the silver method of 
Salkowski, and the latter has recently shown that other nitrogenous 
constituents are also precipitated with Kriiger' s method. 

As Salkowski has not as yet published his new method, that of 
Kriiger- Wulff only will here be considered. 

Method of Kruger-Wulff. The method is based upon the 
observation of Kriiger that copper sulphate and sodium bisulphite will 
completely precipitate uric acid and the alloxur bases in the urine, 
and these only. 1 In the precipitate the amount of nitrogen is then 
determined. In a second portion of urine the uric acid is estimated 
and the corresponding amount of nitrogen deducted from the total 
quantity. The difference will then indicate the amount of nitrogen 
in the form of alloxur bases (B). As an equal mixture of 100 parts 
of xanthin, hypoxanthin, paraxanthin, heteroxanthin, carnin, and 
guanin, moreover, contains 36.295 per cent, of nitrogen, the quan- 

1 This statement is denied by Salkowski. 



372 CLINICAL DIAGNOSIS. 

tity of B in terms of this mixture, which corresponds to the amount 
of B-nitrogen found, is readily determined according to the equation: 

36.295 : 100 : : x : r, and v = 100x , i.e., j = x 2.755, 

where x represents the amount of B-nitrogen found and y the cor- 
responding amount of alloxur bases. 
Reagents required: 

1. A 50 per cent, solution of sodium bisulphite. 

2. A 13 per cent, solution of copper sulphate. 

3. A 10 per cent, solution of barium chloride. 

4. Gunning's mixture. 

Method: One hundred c.c. of urine, which must be free from 
albumin, are brought to the boiling-point and treated with 10 c.c. 
of the bisulphite, and immediately after with 10 c.c. of the copper 
solution. The mixture is allowed to boil for a moment, when the 
originally white precipitate turns brown. Five c.c. of the barium 
solution are then added in order to facilitate the sedimentation of 
the precipitate and its nitration. After two hours' standing the pre- 
cipitate is collected on a folded filter, of Swedish paper, measuring 
about 10 to 12 cm. in diameter, and washed with boiled water, cooled 
to a temperature of 60° C. Filling the filter five times is sufficient. 

The moist filter is placed in a Kjehldal digesting flask of 150 c.c. 
capacity, and treated with Gunning's mixture (see p. 346). For 
practical purposes it is best to treat the moist filter first with the 
sulphuric acid and copper sulphate, and to heat the mixture until 
fumes of sulphuric acid are given off in abundance. The potassium 
sulphate is then added. After heating for an hour or two longer 
— i. e., until the liquid has become entirely clear and almost color- 
less — the residue is further treated as described on p. 346. As the 
method is by no means simple and requires considerable skill, at 
least three parallel estimations should be made and the average 
figure taken. 

The uric acid is best estimated according to Hopkins' method. 
One gramme corresponds to 0.33 gramme of nitrogen. 

The calculation of the amount of B-nitrogen and of alloxur bases 
is then conducted as described above. The average amount of 
B-nitrogen and alloxur bases eliminated in the twenty-four hours 
in health amounts to 0.0481 and 0.1325 gramme respectively. The 
relation of uric acid nitrogen to B-nitrogen varies between 2.1:1 
and 7.6 : 1. 



THE URINE. 373 



Oxalic Acid. 



The origin of oxalic acid in normal urine appears to be twofold, 
one portion being referable to vegetable food ingested, the other 
originating in the body in a manner not definitely understood at 
the present time. It is quite probable, however, that this latter 
portion is derived, to some extent at least, from uric acid through 
a process of oxidation, a view which is supported by the artificial 
production of oxaluric acid from uric acid, the former being like- 
wise a constant constituent of the urine. Oxaluric acid is readily 
decomposed into oxalic acid and urea, as is seen from the following 
equations: 

1. C 6 H 4 N 4 3 + O + H 2 == C 4 H,NA + CON 2 H 4 
Uric acid. Alloxan. Urea. 



2. C 4 H 2 N 2 4 + = 


CO 


,NH.CO 

( i + oo 2 

x NH.CO 




Alloxan. 


Parabanic acid. 






JTO.CO 

3. co; | + H 2 
x XH.CO 


CO— NH- 
CO.OH 


-CONH 2 




Parabanic acid. 




Oxaluric acid. 




CO-XH-CONH 2 
4. 1 + 
CO.OH 


00- 

H 2 0= | 

CO- 


-OH /NH 2 

-^co<; 

-OH X NH 2 


Oxaluric acid. 




Oxalic acid. 


Urea. 



Oxalic acid may also result from an incomplete oxidation of car- 
bohydrates. 

From a pathologic standpoint the study of the excretion of oxalic 
acid is of decided importance. Care should, however, be taken in 
the interpretation of the results reached by a chemical examination, 
as many vegetables are capable of producing an excessive excretion 
of this acid. Among these may be mentioned tomatoes, spinach, 
carrots, celery, string-beans, asparagus, apples, grapes, etc. 

Gastro-intestinal disturbances are very apt to cause an increased 
elimination of oxalic acid, probably in consequence of a defective 
digestion and subsequent oxidation of carbohydrates, the so-called 
nervous oxaluria being probably of this origin. Very interesting 
is the form of oxaluria observed in case3 of transient albuminuria, 
described by Senator and confirmed by v. Noorden and others. To 
this class the so-called Albuminuria and Bright 9 8 Disease of Uric 
Acid and of Oxalic Acid of Da Costa in all probability also belongs. 



374 



CLIXICAL DIAGNOSIS. 



In the chapter on Phosphates it was shown that in diabetes niel- 
litus a certain relation appears to exist at times between the excretion 
of sugar and phosphates, these bodies increasing and decreasing in 
an inverse relation to each other. A similar condition is also noted 
in the excretion of nric acid. In the case of oxalic acid such a 
vicarious elimination, as it were, is likewise not infrequently ob- 
served, and may at times be very pronounced, indicating the exist- 
ence of a probable relation between carbohydrates and oxalic acid. 
The oxalic acid diathesis, or idiopathic oxaluria, must finally be 
considered. In this condition there is associated with a defini:T." 
recognizable increased production a temporary retention, followed 
by an increased elimination of oxalic acid, notwithstanding the fact 
that a perfectly normal diet — 1. e.. one not especially rich in oxaMc- 
acid-containing constituents — may be taken. There can thus be 
no doubt of the occurrence of abnormal metabolic processes in the 
body. These are probably similar to those giving rise to diabetes 
mellitus, there being, as it were, a suspended oxidation in diabetes 
and an insufficient oxidation in the idiopathic oxaluria, the relation 
between the two diseases being further shown by the vicark 
elimination of oxalic acid in diabetes. 

Properties of Oxalic Acid Oxalic acid occurs in the urine 
calcium oxalate, CaCX) 4 , being held in solution by the diacid sodii 

phosphate. It can, hence, be precipi 

tated by diminishing the acidity 

the urine by the addition of a little 

ammonia, or by allowing it to 

exposed to the air. Calcium 03 

when allowed to crystallize out slowly, 

— occurs in the form of well-d< 

stzv ugly refractive octahedra, the 

known envelope forms resulting, 

which the principal axis of tL e 

is placed at right angles to the p] 

of the microscopic slide (Fig. 93). 

Calcium oxalate may always be recognized by its charaetei 

rystals, its insolubility in acetic acid, and its solubility in hydi 

chloric acid. TThen strongly heated it is decomposed into calch 

oxide, carbon dioxide, and carbon monoxide, according to the eqx 

tion: 

CaC 2 4 = CaO -...-.." 



Fig. 98. 




Calcium oxalate crystals. 



THE URINE, 375 

The quantity excreted in the twenty-four hours varies from faint 
trace.- to 20 milligrammes. It must he remembered here that an 
increased or diminished excretion of oxalic acid cannot be determined 
by a microscopic examination of the sediment, as numerous crys- 
tal* of oxalate of calcium may be seen when a quantitative estima- 
tion actually shows a diminution of the normal amount, and vice 
versa. 

Tests for Oxalic Acid. For the detection of calcium oxalate it 
is frequently only necessary to examine the sediment of the urine 
after twenty-four to forty-eight hours, but, as has been pointed out, 
no oxalate crystals may be found even when an abnormally large 
amount can be demonstrated by chemical methods. In such cases 
it Is usually possible to bring about the crystallization of the salt 
by carefully neutralizing the urine with a little ammonia. Should 
this procedure not lead to the desired result, it is best to proceed by 
a method which may at the same time be employed for its quanti- 
tative estimation. 

Quantitative Estimation of Oxalic Acid. Principle: The 
oxalate of calcium occurring in the urine is held in solution by the 
diacid sodium phosphate. If this be removed by means of calcium 
chloride and ammonia, the calcium oxalate is precipitated. By 
heating this strongly it is transformed into calcium oxide. 

As 56 parts by weight of calcium oxide correspond to 128 parts 
by weight of calcium oxalate, the amount of the latter can be 
readily calculated according to the equation: 56 : 128 : : y : x, and 
x = 2 2857y, in which y indicates the amount of calcium oxide 
found in a given amount of urine, and x the corresponding amount 
of calcium oxalate. As 1 molecule of oxalic acid, moreover, corre- 
sponds to 1 molecule of calcium oxalate, the amount of the former 
can be found from that of the latter according to the equation: 
128 : 90 : : y : x, and x=0.703y, in which y represents the 
amount of calcium oxalate found, and x the amount of the corre- 
sponding acid. 

Method: A large amount of urine (600 to 1000 c.c), after having 
been treated with a small amount of an alcoholic solution of thymol, 
- to guard against putrefactive processes, is treated with calcium 
chloride and ammonia added in excess in order to remove the diacid 
sodium phosphate which holds the oxalic acid in solution. During 
this process the oxalate of calcium is thrown down together with 
the phosphates. The precipitate is then carefully treated with an 



376 CLINICAL DIAGNOSIS. 

amount of acetic acid just sufficient to dissolve it. As calcium 
oxalate is insoluble in acetic acid, it gradually separates out. To 
this end the mixture is allowed to stand for twenty-four hours, the 
addition of the thymol preventing the development of bacteria. At 
the end of this time the calcium oxalate is filtered off through a 
small filter. It is then washed with a small amount of water and 
dissolved with a few drops of hydrochloric acid, any uric acid that 
may have separated out being left behind. The filtrate is then 
treated with a small amount of very dilute ammonia, so as to render 
the solution slightly alkaline. After standing for twenty-four hours 
the calcium oxalate will have separated out, and is collected upon 
a small filter, the weight of the ash in this being known. After 
washing with water the contents of the filter are dried and incin- 
erated in a crucible, heating strongly for about twenty minutes, 
whereby the oxalate is transformed into the oxide. From the 
weight of this the corresponding amount of oxalic acid is readily 
calculated according to directions previously given. 

Albumins. 

The albumins which may be met with in the urine are: Serum- 
albumiu, serum-globulin, albumoses (peptones), haemoglobin, nucleo- 
albumin, fibrin, and histon. Of these, serum-albumin is the most 
important from a clinical standpoint, and whenever in the following 
pages the term albuminuria is employed it should be remembered 
that serum-alb uminuria is meant. 

Serum-albumin. The question whether or not serum-albumin 
occurs normally in the urine — i. e., under conditions strictly physio- 
logic in their nature — has been much disputed, it being claimed by 
some that traces may temporarily be met with in many individuals, 
particularly after severe muscular exercise, cold baths, mental 
labor, severe emotions, during menstruation, digestion, etc. This 
so-called physiologic albuminuria mostly occurs in young adults, 
and is usually, if not always, of brief duration, the urine, it is 
claimed, being otherwise normal — i. e., of normal amount, appear- 
ance, specific gravity, and composition, and free from abnormal 
morphologic constituents, such as casts, red corpuscles, leucocytes, 
and epithelial cells. The persons examined must, furthermore, be 
entirely free from subjective or objective abnormalities. 

The existence of a physiologic albuminuria, on the other hand, is, 
denied, and the occurrence of serum-albumin at least regarded as 






THE URINE. 377 

pathologic in every case. The author has never been able to con- 
vince himself of the presence of serum-albumin in the urine under 
strictly physiologic conditions, and it has already been pointed out 
elsewhere that severe muscular and mental labor, severe mental 
emotions, eold baths, etc., can hardly be regarded as physiologic 
atimuli for all persons. The albuminuria so often observed during 
the first days of life, at which time sediments of uric acid and 
urates, mucus, epithelial cells from the different portions of the uri- 
nary tract, and even casts may also be seen, constituents which in 
adults would rightly be regarded as abnormal, has also been brought 
forward in support of the theory of a physiologic albuminuria. 
There can be no doubt, however, that this form of albuminuria is 
referable to the profound changes that take place in the circulatory 
system after birth, and to some extent perhaps also to the well- 
known uric-acid infarctions so frequently seen in the kidneys of the 
newly born, so that it would probably be better and more in accord 
with the teachings of pathology to regard this albuminuria as ab- 
normal. 

The more closely the subject of the so-called physiologic albu- 
minuria is studied the more improbable does its physiologic nature 
appear, and a more detailed study of the metabolic processes, it may 
be confidently asserted, will untimately lead to the conclusion that 
the presence of albumin in every case is a pathologic phenomenon. 

The association of an increased elimination of urea and uric acid 
with albuminuria in apparently healthy individuals was noted 
twenty five years ago, but received comparatively little attention. 
More recently, Da Costa, in a paper entitled " The Albuminuria 
and Bright' s Disease of Uric Acid and Oxalic Acid," pointed out 
the existence of albuminuria associated with lithuria and oxaluria. 
Personal observations have led the author to look upon this form 
of albuminuria as being of common occurrence, and while in almost 
every case the albumin can be caused to disappear from the urine 
by proper diet and exercise, there can be no doubt that if neglected 
granular atrophy may ultimately result. 

An albuminuria may at times be observed in anaemic children 
and adolescents, and particularly in masturbating boys of the 
mouth-breathing type, but it can hardly be regarded as physiologic. 
The same may be said of the albuminuria of pregnancy and partu- 
rition. 

The course which these various forms of what should be termed 



378 CLINICAL DIAGNOSIS. 

functional albuminuria, in which the amount of albumin rarely 
exceeds 0.1 per cent, may take, is very interesting. The elimi- 
nation of albumin may thus be quite transitory on the one hand, 
as when following severe mnseular exercise, cold baths, and the 
like. It may, however, also last for several days or even wfeks 
and be followed by a disappearance of the albumin for a variable 
length of time, and again by its reappearance and continuance for 
days and weeks. The term intermittent albuminuria has been ap- 
plied to this latter type. At times the albuminuria may follow a 
definite course, disappearing and reappearing with such regularity 
that it has not improperly been styled cyclic albuminuria. In this 
form the albumin generally disappears from the urine during the 
night, or during a prolonged rest in bed, reappearing during the 
day, the erect posture apparently favoring its reappearance ; the 
term postural albuminuria has hence also been suggested for this 
form. Osswald. who made a careful study of cyclic albuminuria in 
Iviegel's clinic, regards its occurrence as distinctly pathologic, and 
as indicating the existence of nephritis. Eemembering the im- 
portance of the subject, it may not be out of place to enumerate 
the reasons which led Osswald to this conclusion: 

1. The patients generally come to the physician complaining of 
certain definite symptoms which are the same as those noted in 
sases of true nephritis. At times, however, no complaints are 
made, because the patients have Teasons for concealing these as in 
examinations for life-insurance), or because they are for the time 
being absent. 

2. The subjective complaints, as well as the anaemia so frequently 
observed in such cases, generally disappear, together with the albu- 
min, under suitable treatment, to reappear when the anemia again 
becomes marked. 

3. In many a history of an antecedent nephritis, the result of 
scarlatina or diphtheria, may be obtained, as in three cases of Heub- 
ner, in fourteen cases out of twenty described by Johnson, etc. In 
some also a direct transition from an acute nephritis to the c} 
form of albuminuria has been noted. Where this was not possible 
the history of an acute infectious disease or an angina, that had been 

: looked in the clinical history, must be regarded as a possible 
eune. 

4. The absence of morphologic elements, especially tube-easte, i 
does not negative a nephritis. A large number of cases, fa : - 



THE URINE. 379 

over, have recently been observed in which casts were repeatedly 
found. 

5. A cyclic albuminuria may be observed in many cases of chronic 

nephritis. 

6. Marked organic abnormalities (such as heart-lesions) need not 
be demonstrable, as they may be absent for a long period of time 
or may be unrecognizable. 

Senator's statement, that the existence of a physiologic albuminuria 
is proved by the fact that the morphologic constituents of the primi- 
tive nubecula contain albumin, requires no further criticism, and 
should be regarded as a misconstruction of the main point at issue — 
a mere sophism — and Posner's observations, in view of the researches 
of Malfatti, which tend to show that the body obtained by Posner 
was not serum-albumin, but a nucleo-albumin, may now be regarded 
as erroneous. 

In conclusion, it may safely be said that a transitory, intermittent, 
and cyclic albuminuria is not infrequently observed in apparently 
heaHhy individuals, but that the facts so far brought forward do 
not warrant the assumption that such forms of albuminuria are 
physiologic. 

It would lead too far to enter into a detailed consideration of the 
various causes that have from time to time been suggested as an 
explanation of the fact that albumin does not occur in the urine 
under normal conditions. There can be no doubt, however, that 
the integrity of the epithelial lining of the glomeruli and the con- 
voluted tubules must be regarded as the principal factor which pre- 
vents the albumin of the blood from passing into the urine. When 
the readiness with which the glandular structure of the kidney 
responds to any abnormal stimulation is considered, it is easily 
understood how an albuminuria may be evoked in many different 
ways. Aside from acute and chronic inflammatory processes in 
the widest sense of the word, an albuminuria may be the result of 
circulatory disturbances in the kidneys of whatever kind — i. e., the 
result of amemia, as well as of hyperemia. In many and perhaps 
the majority of cases in which what Bamberger terms a hemato- 
genous albuminuria occurs, we have direct evidence of the existence 
of circulatory disturbances, as in cases of uncompensated valvular 
lesions, weak heart, emphysema, hepatic cirrhosis, etc. In other 
cases, however, the existence of such disturbances can only be sur- 
mised, and the question whether or not, for example, the albumin- 



380 CLINICAL DIAGNOSIS. 

uria observed in the various infectious diseases is referable to cir- 
culatory abnormalities, or to a direct irritative action of microbic 
poisons upon the renal parenchyma, must still remain an open one. 

From personal studies in connection with the functional albu- 
min una of Da Costa, it seems not unlikely that in many cases in 
which obscure circulatory disturbances are supposed to exist and 
made responsible for an existing albuminuria, this is referable rather 
to the strain thrown upon the kidneys by the continued elimination 
of abnormally large quantities of organic material, the quantity of 
water being at the same time proportionately small. 

If it be remembered, furthermore, that injuries affecting certain 
portions of the brain are followed by albuminuria, and that such 
may be artificially produced by a piqure, analogous to the glycosuric 
piqure of C. Bernard, still another factor is given which may pos- 
sibly enter into the causation of albuminuria. 

Obstruction to the outflow of urine from the kidneys has also 
experimentally been shown to lead to albuminuria, an observation 
with which clinical experience is in perfect accord. 

Finally, an abnormal composition of the blood may at times cause 
albuminuria. 

In passing on to a more detailed study of the various pathologic 
conditions in which an elimination of albumin may be noted, 
an attempt will be made to classify the various forms of albumin- 
uria in accordance with the more general considerations set forth 
above. It should be remembered, however, as already indicated, 
that it may be very difficult, if not impossible, to assign one single 
cause to a given clinical case, as several factors may at the same 
time be concerned in the production of the albuminuria. 

1. Functional albuminuria. Under this heading may be com- 
prised the various forms of ^physiologic^ albuminuria which 
have already been considered. 

2. The albuminuria associated with organic diseases of the kidneys ; 
viz., acute and chronic nephritis, renal arterio-sclerosis, amyloid 
degeneration of the kidneys. 

In acute nephritis, albuminuria, usually of considerable intensity, 
is a constant and most important symptom. The amount eliminated 
is generally proportionate to the intensity of the disease, but varies 
within fairly wide limits, generally from 0.3 to 1 per cent, cor- 
responding to a daily excretion of from 5 to 8 grammes. Much 
larger quantities, it is true, are at times excreted, but it may be 



THE URINE. 381 

definitely stated that the daily loss of albumin seldom exceeds 20 
grammes. 

In chronic parenchymatous nephritis the elimination of albumin 
is likewise constant, and the amount excreted in severe cases may 
even exceed that observed in the acute form. An elimination of 
from 15 to 30 grammes, viz., 1.5 to 3 per cent, by weight, is fre- 
quently observed. 

In the ordinary form of chronic interstitial nephritis the elimina- 
tion of albumin is, as a general rule, slight, rarely amounting to 
more than 2 to 5 grammes pro die. At the same time it is not 
unusual to meet with an apparent absence of albumin, if the more 
common tests (see below) be employed. If it be remembered that 
very often the diagnosis of the disease is directly dependent upon 
the demonstration of the presence or absence of the albumin, the 
necessity of frequent examinations and the employment of more 
delicate tests, particularly of the trichlorace tic-acid test, as well as 
of a microscopic examination is at once apparent. This is of even 
more moment in the renal arterio-sclerosis of Senator, in which 
albumin by the ordinary tests is probably not demonstrable in the 
majority of cases, and in which even the trichloracetic-acid test 
may not be of service, and casts absent. 

Amyloid degeneration of the kidneys, in the absence of inflamma- 
tory processes, is accompanied by a condition of the urine closely 
resembling that observed in the ordinary form of chronic interstitial 
nephritis. A total absence of albumin, however, is less frequently 
noted, while an amount varying between 1 and 2 per cent, is not 
at all uncommon. It will be shown later on that in this condition 
considerable amounts of serum-globulin are excreted in addition to 
the serum-albumin; larger amounts, in fact, than are generally 
observed in this form of chronic renal disease, so that Senator sug- 
gests that such a relation, in the absence of an acute nephritis or an 
acute exacerbation of a chronic nephritis, may be of a certain diag- 
nostic value. 

3. Febrile albuminuria. That albuminuria may occur in almost 
any one of the various febrile diseases is a well-known fact, but it 
is important to remember that, while such an albuminuria may at 
times be referable to a true nephritis developing in the course of 
or during convalescence from an acute febrile disease, such is the 
exception, and not the rule. Under this heading only that form 
will be considered which is not associated with distinct changes 



382 CLINICAL DIAGNOSIS. 

affecting the renal parenchyma, and which generally appears during 
the height of the disease only, to disappear again with a return of 
the temperature to normal limits. As has already been mentioned, 
it is often very difficult, if not impossible, to assign a definite cause 
for the occurrence of an albuminuria of this character, and in all 
probability several factors are in operation at the same time. In 
the beginning of the disease, when, as a rule, the blood-pressure is 
increased, the albuminuria may be referable to an ischsemia of the 
kidneys, as the increased pressure in fever, according to Cohnheim 
and Mendelson, is largely referable to spasm of the arterioles. 
Later on, or in the beginning of cases in which especially severe 
intoxication exists, the blood-pressure may be subnormal, and the 
albuminuria be due to this cause — i. e., a hypersemic condition of 
the kidneys. As a matter of fact, it has been experimentally 
demonstrated that both ansemia and hypersemia of the kidney- 
structure may lead to albuminuria. On the other hand, it is not 
at all unlikely that the strain thrown upon the kidneys by an 
excessive elimination of organic material, in the absence of a corre- 
spondingly large quantity of water, may produce albuminuria. The 
author has repeatedly seen the functional albuminuria of the type 
described by Da Costa disappear during the administration of a diet 
relatively poor in nitrogen, an increased diuresis being at the same 
time effected by the consumption of large amounts of water. 

In those grave cases of typhoid fever, furthermore, which are 
characterized by high fever and pronounced nervous symptoms it 
would appear quite likely that the albuminuria, which in these 
cases is particularly marked, is referable to a direct influence upon 
the central nervous system, and in some cases, at least, also depen- 
dent upon an irritant action on the part of the microbic poisons 
circulating in the blood upon the renal epithelium. The character 
of the albuminuria will largely depend upon the intensity of the 
intoxication; in other words, upon the amount of bacterial poison 
present at any one time in the blood. 

Notwithstanding the statements to the contrary, albuminuria may 
be regarded as a constant symptom of typhoid fever, as has been 
definitely demonstrated by Grubler and Robin. It is difficult to 
say why other observers found this in only a comparatively small 
percentage of cases, but it is not unlikely that this was owing td 
a lack of uniformity in methods, it being presupposed also that 
observations of this kind can only be decided by daily examina- 



THE URINE. 383 

(ions. According to Robin, the trace of albumin which is at times 
observed during the first week of the disease is an albumose, while 
later on serum-albumin is quite constantly found, the amount in- 
creasing with the intensity of the morbid process, the highest figures 
being reached in fatal cases. The more severe the disease the 
earlier does albumin appear in the urine, it being remembered, 
however, that reference is had only to those cases in which distinct 
renal changes are not demonstrable. Toward the termination of 
the fastigium the amount of albumin generally undergoes a certain 
diminution, and may even disappear entirely. This diminution, 
however, is only temporary, and in severe cases the albumin again 
increases in amount during the period of the great variations in the 
temperature. In light cases an increased elimination also takes 
place at this stage, but is soon followed by a decrease, after which 
time only traces can be demonstrated in the urine. In some also 
it disappears entirely, but it is rare, according to Robin, to meet 
with cases in which a trace at least does not reappear during con- 
valescence. 

In light cases the albuminuria rarely persists longer than the fifth 
or eighth day of convalescence, and Robin even goes so far as to say 
that a relapse may frequently be predicted if the albuminuria does 
not disappear at this time. A limited number of personal observa- 
tions have borne out the correctness of this view, and in one case in 
which a relapse occurred as late as the fifteenth day of convalescence 
traces of albumin could be demonstrated during the entire period. 
In severe cases, on the other hand, the albumin persists for a vari- 
able length of time, rarely disappearing before the tenth day of 
convalescence. At times an increase is seen during convalescence, 
where only traces have previously been observed. It is this form 
which the French generally speak of as colliquative albuminuri<(. 
AVhile this form is principally observed in typhoid fever, it is not 
unusual to meet with it during the convalescence from various other 
acute diseases. Care must be taken not to confound the albumin- 
uria so frequently seen during the convalescence from typhoid 
fever, referable to a pyelitis, with the form just described. 

From the following table, constructed from data given in Robin's 
most excellent work on the urine of typhoid fever and other acute 
infectious diseases which may be associated with a typhoid condi- 
tion, an idea may be formed of the occurrence of albuminuria, as 
well as of its degree of intensity in these diseases: 



384 CLINICAL DIAGNOSIS. 

Acute miliary tuberculosis: Albumin much less frequent than in 
typhoid fever; when present it is rarely found in the abundance so 
characteristic of the fatal cases of the latter disease. 

Pneumonia: Albumin is as uniformly present as in typhoid fever. 
At times very abundant. 

Grippe: Albumin infrequent; present in about 20 per cent, of 
the cases and only in traces. 

Herpetic fever: Albumin never present in large amounts. 

Embarras gastrique: Albumin rarely present. 

Adynamic enteritis of adults: Albumin almost always present. 
bat usually only in traces 

Cerebrospinal meningitis: Albumin in fairly large amounts. 

Vegetative endocarditis: Albumin very abundant in about 14 
per cent., evident in 44 per cent., and traces in 42 per cent. 

Acute articular rheumatism: Albumin present in about 40 per 
cent. 

Rubeola: Albumin usually absent in light cases, but present in 
the more severe and complicated forms. 

Intermittent fever: Albumin variable. 

In conclusion, it may be said that practically every acute febrile 
disease, even simple follicular tonsillitis, may be accompanied by 
albuminuria in the absence of definite changes affecting the renal 
parenchyma. Its occurrence in an individual case is probably 
dependent, to a very large degree, upon the intensity of the in- 
toxication. ^Vhile it is eenerallv an easv matter to distinguish 
between this form of albuminuria and that associated with distinct 
organic changes in the kidneys, considerable difficulty may at times 
be experienced, a question which will be dealt with later on. 

4. Albuminuria referable to circulatory disturbances. To this class 
belongs the albuminuria so frequently observed in cardiac insuffi- 
ciency referable to valvular lesions, degeneration of the heart-muscle 
from whatever cause, disease of the coronary arteries, etc., as well 
as in cases of impeded pulmonary circulation affecting the general 
circulation through the right heart, and, finally, in conditions asso- 
ciated with local circulatory disturbances, such as compression of 
the renal veins by a pregnant uterus, tumors, etc. It has already 
been pointed out that febrile albuminuria also may, to a certain 
extent at least, be referable to such causes; i. e., an ischsemia or 
hyperemia of the kidneys, produced by an increased or diminished 
blood-pressure. The albuminuria observed in cases of cholera 



THE URINE. 385 

infantum, the simpler forms of intestinal catarrh, and in cholera 
Asiatica particularly, are undoubtedly dependent upon such causes. 
The occurrence of albuminuria after cold baths, as stated above, is 
regarded by many as a " physiologic" phenomenon, a view which 
should be rejected, however, as there can be but little doubt that 
this form of albuminuria also is referable to circulatory disturb- 
ances. The quantity of albumin found under these circumstances 
varies considerably, but rarely exceeds 0.1-0.2 per cent., unless 
indeed the disease has advanced to a point where distinct changes 
in the renal parenchyma have resulted. 

5. Albuminuria referable to an impeded outflow of urine. Clinic- 
ally, albuminuria referable primarily to an impeded outflow of urine 
from the kidneys is probably of more frequent occurrence than is 
generally supposed, and especially in women, in whom Kelly and 
others have demonstrated the frequent existence of ureteral stenoses. 
A complete blocking of the excretory duct, on the other hand, is 
rarely seen, but may be caused by the impaction of a renal calculus, 
the pressure of a tumor, or following certain gynaecological opera- 
tions in which the ureter is accidentally caught in a suture, etc. It 
has also been suggested that the albuminuria of pregnancy may be 
due to compression of an ureter, but it is more likely that other 
factors are here of moment — I e., compression of the renal arteries, 
as well as of the veins. 

6. Albuminuria of hozmic origin. It was formerly quite gener- 
ally supposed that Bright' s disease was dependent upon certain 
abnormalities of the blood, a view which has not only never been 
disproved, but which is actually gaining in importance from day to 
day. According to Semmola, Bright' s disease is primarily due 
to an abnormal power of diffusion on the part of the albumins of 
the blood, which are elimintaed by the kidneys as waste material. 
As a result of the excessive amount of work thus done definite renal 
changes are finally produced. According to his theory, then, the 
albuminuria is the primary factor in the causation of nephritis, a 
view which, notwithstanding many assertions to the contrary, has 
certainly many points in its favor. Should this hypothesis hold 
good, Senator is correct in asserting that an albuminuria of func- 
tional origin, so to speak, must precede the occurrence of the nephri- 
tis proper. He appears to doubt the occurrence of a prenephritic 
albuminuria, however. In this connection it is interesting to note 
that definite renal changes have actually been observed to follow 

25 



386 CLINICAL DIAGNOSIS. 

an apparently f unctional albuminuria (Da Costa), demonstrating the 
possibility of such an occurrence. Further researches, however, 
are urgently needed in this direction, and Semmola's view, as well 
as all others so far proposed, can only be regarded as an hypothesis. 
Even if such blood-changes as those which Semmola suggests should 
not exist, there can be little doubt that true nephritis is depen- 
dent upon an acute or chronic dyscrasia of the blood, either in the 
sense of an abnormal mixture of the normal elements or of the 
presence of abnormal constituents, and notably of poisons. The 
same considerations undoubtedly also apply to various other forms 
of albuminuria, in so far as these are not the direct result of circu- 
latory disturbances. 

Clinically, albuminuria of haemic origin is observed in various 
diseases of the blood, such as purpura, scurvy, leukaemia, pernicious 
anaemia, and also in cases of poisoning with lead and mercury, in 
syphilis, jaundice, diabetes, following the inhalation of ether and 
chloroform, etc. The albuminuria associated with an excessive 
elimination of uric acid and oxalic acid, and, according to personal 
observations, with an excessive elimination of organic material in 
general, notably of urea, probably also belongs to this class. 

7. Toxic albuminuria. It has already been stated that the albu- 
minuria of acute febrile diseases may to a certain extent be referable 
to a direct irritant action on the part of bacterial poisons upon the 
renal parenchyma. Poisoning with cantharides, mustard, oil of tur- 
pentine, potassium nitrate, carbolic acid, salicylic acid, tar, iodine, 
petroleum, phosphorus, arsenic, lead, antimony, alcohol, and min- 
eral acids produces albuminuria. In all probability, however, the 
albuminuria here observed is referable not only to a direct irritant 
action upon the glandular epithelium of the kidneys, but also to 
circulatory disturbances. 

8. Neurotic albuminuria. It is claimed by some that albumin, 
usually in small amounts, is eliminated in epilepsy after every 
attack, while others either entirely deny its occurrence under such 
conditions or regard it as exceptional. In a number of cases in 
which the author had occasion to examine the urine voided after 
an attack albumin was usually absent. It must be stated, however, 
that the seizures in these cases were comparatively mild, and that 
an examination for semen was unfortunately not made in those 
cases in which only traces of albumin could be demonstrated. A 
recent examination of the urine voided by an epileptic, after having i 



THE URINE. 387 

been in the epileptic state for more than forty-eight hours, showed 
the presence of a small amount of albumin, associated with an enor- 
mous elimination of uric aeid, as well as a large excess of urea. 
Somen was absent. A transient albuminuria has also been noted 
in eases of progressive paralysis, mania, tetanus, delirium tremens, 
apoplexy, migraine, Basedow's disease, etc. 1 

Although albuminuria may apparently be artificially produced by 
injuries affecting a certain point in the floor of the fourth ventricle, 
analogous to the production of glycosuria (see Glycosuria), it would 
probably be going too far to assume the existence of a certain spe- 
cific centre, stimulation of which would cause the appearance of 
albumin in the urine. While the influence of the nervous system 
in preventing the passage of albumin through the glomeruli under 
normal conditions is undoubted, it would appear more likely that 
the albuminuria following injuries to the central nervous system is 
referable to circulatory disturbances in the kidneys secondary to 
lesions in the brain, especially in the medulla. The albuminuria 
observed in certain neurotic individuals, on the other hand, is prob- 
ably more frequently associated with metabolic abnormalities and 
of haemic origin. 

9. A digestive albuminuria has also been described, but need not 
be considered in detail. Suffice it to say that it may follow the 
ingestion of excessive amounts of cheese, eggs — particularly when 
taken raw — beef, etc. The author has seen albuminuria follow a 
free indulgence in root beer. It is, of course, difficult to explain 
such occurrences; but, bearing in mind the fact that albuminuria 
very often follows the ingestion of such articles almost immediately 
and before they have actually had time to become absorbed, it is 
hardly justifiable to refer this form to the existence of a hyperalbu- 
minosis. It would appear more rational in such cases, as Senator 
has suggested, to think of reflex or vasomotor or trophic changes 
affecting the kidneys; while in other cases, in which the albumin- 
uria does not follow the ingestion of such articles of food immedi- 
ately, it is quite probable that this may be dependent upon certain 
metabolic abnormalities affecting the normal composition of the 
blood. 2 



1 Recently the author observed the occurrence of albumin in the urine of a case of cerebral 
sarcoma. 

- The albumin which is eliminated after the ingestion of much egg-albumin, however, does 
not belong to this category. 



388 CLINICAL DIAGNOSIS. 

In the account given of the occurrence of albuminuria and its 
possible causes reference has been only had to & purely renal albu- 
minuria. It should be remembered, however, that the origin of 
the albumin may often be extremely difficult to determine, as albu- 
minous material, such as blood and pus, may become mixed outside 
of the glandular portion of the kidneys with what would otherwise 
have been a perfectly normal urine, and that such an admixture 
may not only take place in the ureters, the bladder, and the urethra, 
but even in the pelvis of the kidney. 

The term accidental albuminuria is applied to a condition in which 
albuminous material becomes mixed with a urine beyond the kid- 
neys which has been secreted free from albumin, as in cases of cys- 
titis and urethritis, or whenever semen has entered the urine. Such 
an admixture of pus, blood, lymph, or chyle may, however, occur 
in the kidneys, when the albuminuria is termed accidental renal 
albuminuria, an example of which is frequently seen in the slight 
degree of albuminuria referable to pyelitis, during the convalescence 
from typhoid fever. By a mixed albuminuria a ad a mixed renal 
albuminuria, on the other hand, are meant conditions in which the 
source of the albumin is twofold, renal and extrarenal in the first 
instance, parenchymal and extraparenchymal in the second, ex- 
amples being the albuminuria of cystitis combined with nephritis 
and pyelonephritis, respectively. 

It is manifest, of course, that in every instance in which albumin 
is found in the urine its origin should be ascertained. While this 
question is usually readily decided by a microscopic examination 
of the urine, considerable difficulty may occasionally be experi- 
enced. It is a well-known fact that in the urine of females a trace 
of albumin may frequently be detected which is not due to any 
existing lesion of the urinary organs, but to an admixture of vaginal 
discharge, of blood during the process of menstruation, and in mar- 
ried women of semen. Whenever, therefore, doubt is felt as to the 
origin of the albumiu, the specimen for examination should be 
obtained by the catheter, care being taken previously to cleanse the 
vulva. In males albumin may be referable to a gonorrhoea! ure- 
thritis, and only recently a case was observed in which a gentleman, 
who had been rejected by a life-insurance examiner on account of 
the presence of albumin in his urine, was discovered to have a free 
urethral discharge, the albuminuria clearing up on treatment of his 
gonorrhoea. In such cases it is well to let the patient flush out his 



THE URINE. 389 

urethra first, and make use of the portion last passed for examination. 
Very often, however, the conditions are more complex, it being uncer- 
tain whether the albumin is due to a cystitis or whether it has come 
from the kidneys. Here a careful microscopic examination is called 
for, and will in the majority of instances decide the question. At 
other times even then we may be left in doubt, when recourse should 
be had, if at all possible, to catheterization of the ureters. The latter 
procedure is usually called for in obscure cases of pyuria and of 
hematuria, in which it is necessary not only to ascertain the origin 
of the pus or blood, but also to determine the kidney from which 
this has proceeded, and, if one be found to be diseased, the con- 
dition of the other. 

As far as the amount of albumin which may be eliminated in the 
twenty-four hours is concerned, an excretion of less than 2 grammes 
may be regarded as insignificant, 6 to 8 grammes as moderate, and 
10 to 12 grammes or more as excessive. An excretion of 20 to 30 
grammes must be considered as very exceptional. An elimination 
of more than this amount probably never occurs. 

Other albumins which may occur in the urine at times, as already 
indicated, are serum-globulin, albumoses, viz., peptones, haemoglo- 
bin, fibrin, mucin (nucleo-albumin), and histon. 

Serum-globulin. It has been pointed out that serum-globulin 
is found in the urine together with serum-albumin in large amounts 
in cases of amyloid degeneration of the kidneys, and, according to 
Senator, a ratio between the amounts of these two albumins of 
1 : 0.8 : 1.4 may be regarded as a fairly constant symptom of this 
disease, and of some diagnostic importance. There seems to be no 
doubt, however, that serum-globulin occurs in the urine, although 
in much smaller quantities than in the disease mentioned, whenever 
-'•rum-albumin is eliminated, and so far not one case of pure globu- 
linuria has been reported, a fact which is not surprising, as there is 
no reason why only one albumin present in the blood should pass 
through the kidneys. 

Albumoses (peptones). The presence of albumoses in the urine 
has frequently been observed, but is probably more frequently over- 
ly ►ked, as the bodies in question are not precipitated upon boiling. 
The factors which cause their appearance in the urine are probably 
Bimilar to those noted in connection with peptonuria, and will be 
presently considered. Suffice it to say that albumoses have been 
observed in a variety of diseases, such as multiple myelomata of the 



390 CLINICAL DIAGNOSIS. 

bones, dermatitis, intestinal ulceration, liver-abscess, croupous pneu- 
monia, septicaemia, carcinomatous peritonitis, apoplexy, heart-dis- 
ease, pleurisy, caries, puerperal parametritis, endocarditis, typhoid 
fever, diphtheria, pyaemia, nephritis, phthisis, measles, scarlatina, 
leukaemia, urticaria, acute yellow atrophy, various psychoses, etc. 
Very frequently albumosuria accompanies albuminuria, a condition 
which has been termed mixed albuminuria by Senator. In this 
connection it is interesting to note that albumosuria may alternate 
with albuminuria, and precede as well as follow the latter, and in 
any case in which albumoses are demonstrable in the urine the 
appearance of albumin should be expected. 

Albuminous bodies not coagulable by heat, and in their general 
behavior resembling peptones, have repeatedly been seen in urines 
when Hofmeister's method of testing for peptones was employed, 
and various forms of so-called peptonuria have since been de- 
scribed. An elimination of such bodies has been noted in condi- 
tions associated with large accumulations of pus within the body, 
it being supposed that the peptonuria observed in such cases was 
referable to a disintegration of the pus-corpuscles and a resorption 
into the blood of the peptone contained in these. This form of 
peptonuria was hence termed pyogenic peptonuria. A hepatogenic 
form has been likewise described in connection with diseases of the 
liver, notably acute yellow atrophy. It was formerly thought that 
peptones were retransformed, so to speak, into albumins by the 
liver, and the occurrence of peptonuria in diseases of this organ was 
explained by the inability on its part to cause this transformation, 
the peptones accumulating in the blood and being excreted in the 
urine. Later researches, however, have shown that the transfor- 
mation of peptones into albumins takes place in the intestinal 
mucosa, and that the liver apparently has no part in this process, 
so that an explanation of this form is still wanting. An enterogenic 
form has been noted in various diseases of the intestinal tract, such 
as typhoid fever, tubercular ulceration, carcinoma, etc., in which 
it was supposed that peptone is either directly absorbed from the 
disintegrating pus, or that the intestine itself has lost the power of 
causing its transformation into albumin. A histogenic or hemato- 
genic origin was further ascribed to the peptonuria seen in cases of 
scurvy, various forms of poisoning, during the puerperal period, 
pregnancy, particularly following the death of the foetus, in various 
psychoses, etc. Finally, a renal and vesical form of peptonuria was 



THE URINE. 391 

noted in which peptones were formed in albuminous urines either 
in consequence of the presence of enzymes or the occurrence of 

putrefaction. 

More recently, however, since our conception of the nature of 
peptones has changed — it being quite generally accepted at the 
present day that true peptones are not precipitated by ammonium 
sulphate — investigations have shown that in all cases in which the 
presence of these bodies had been previously assumed true peptones 
are actually not present, but that the bodies in question are propep- 
tones or albumoses. According to Killings definition of peptones, a 
peptonuria hence does not exist. 

In the differential diagnosis of suppurative meningitis a positive 
peptone-reaction in the older sense of the word, according to Sen- 
ator, speaks strongly in favor of the existence of this disease, a 
point which at times may undoubtedly be of great importance. In 
support of this view he cites the case of a young man, the subject 
of a median otitis of long standing, in which symptoms pointing to 
a meningitis — viz., fever, headache, and pains in the neck — were 
present, but in which no " peptonuria' ' was found to exist, and in 
which an operation revealed the presence of a cholesteatoma. 

A digestive form of albumosuria has recently been announced, 
where albumoses appear in the urine after their ingestion in large 
quantities, and it is claimed that this is only observed in cases of 
ulcerative disease of the intestinal tract. Only a positive result, 
however, is of value. 

Haemoglobin. Under normal conditions the disintegration of 
red blood-corpuscles constantly taking place in the body never 
results in such a degree of haemoglobinaemia as to be followed by 
au elimination of haemoglobin in the urine. Whenever for any 
reason the destruction of red corpuscles is so extensive, however, 
that the liver is unable to transform into bilirubin all the blood- 
coloring matter set free, hcemoglobinuria will occur. While these 
factors, then — i. e., an excessive destruction of the red blood cor- 
puscles and an insufficiency on the part of the liver — must be 
regarded as explaining every case of hemoglobinuria, our knowl- 
edge of the ultimate causes of such excessive disintegration, as 
well as the manner in which these operate, is as yet very limited. 
Formerly the term haematinuria was applied to this condition. It 
was shown, however, that the pigment eliminated is in reality not 
hse matin, but usually rnethaemoglobin and only at times hsemoglo- 



892 CLINICAL DIAGNOSIS. 

so that the term haemoglobinuria is also, to a certain extent, 
ill chosen. 

M :st frequently to be observed, perhaps, is the haemoglobinuria 
produced by certain poisons, such as potassium chlorate, arseni- 
uretted hydrogen, sulphuretted hydrogen, pyrogallic acid, naphthol, 
hydrochloric acid, tincture of iodine, carbolic acid, carbon mon- 
oxide, etc. , and also by morels (Helvella esculenta). 

Quite familiar is the haemoglobinuria observed following trans- 
fusion of the blood of animals into man, such as that of the calf 
and lamb; also the form seen in cases of extensive burns and inso- 
>n. 

'VThile haemoglobinuria may occur in the course of any one of the 
specific infe::: as -eases, such as scarlatina, icterus gravis, variola 
haemorrhagic: ty| h id fever, yellow fever, etc., it is said to be esj e- 
cially frequent in eases of malarial intoxication. This view is not 
oted by many, Osier, among others, thinking that it has fre- 
quently been confounded with malarial haematuria. The author 
has never seen a single instance of malarial haemoglobinuria, and 
believes that in our more temperate zones it scarcely ever occurs. 
B: srianello asserts that it is likewise rare in Italy, more common 
in Sicily and Greece, and very common in the tropics. According 

the same observer, haemoglobinuria only occurs in infections with 
the aestivo-autumnal parasite. A haemoglobinuria due to quinine 
is likewise -aid to exist, but apparently never occurs, excepting in 
atiente who are suffering, or who have recently suffered, from 
malarial fever. In our country this form is rare also. On the 
other hand, there can be no doubt, to judge from the literature 
upon the subject, that syphilis may, under certain conditions, be a 
potent factor in the production of haemoglobinuria. This appears 
to be particularly true of cases of so-called paroxysmal haemoglo- 
binuria, a condition in which bloody urine is voided from time to 
time, the attacks being frequently preceded by chills and fever, so 

- slosely : simulate malarial fever. Other factors, also, not; 
cold, appear to be concerned in the production of this form. 

The occasional occurrence of haemoglobinuria in cases of Ray- 
naud's disease, coincident with attacks of an epileptiform chara:: 
has been referred to in the chapter on Blood. (See p. 36). 

Haemoglobinuria has been observ - : leukaemia com- 

plicated by icterus. 

Fiually. an epidemic hemoglobinuria has been described as occur- 



THE URINE. 393 

ring in the newborn, associated with jaundice, cyanosis, and nervous 
symptoms; of its causation, however, we are still in profound ignor- 
ance. 

While hemoglobinuria is fairly uncommon, hcemaluria is fre- 
quently observed, and will be considered later on, as its recognition 
is not dependent upon the demonstration of the albuminous body, 
" haemoglobin," alone in the urine, but upon the presence of red 
corpuscles, which in hemoglobinuria are either absent or present in 
only very small numbers. 

Fibrin. The occurrence of fibrin in the urine presupposes the 
presence of fibrinogen, a fibrinogenic ferment, and probably also 
of serum-globulin, and is seldom seen. According to Neubauer and 
Vogel, the fibrin may occur either as coagulated fibrin or in solu- 
tion. In the former condition it is at times observed in the form 
of blood-coagula, when its significance is essentially the same as that 
of hematuria in general, although it must be remembered that the 
usual form of hematuria is not associated with the presence of 
coagula. Colorless coagula of fibrin are only seen in cases of chyl- 
uria or diphtheritic inflammation of the urinary passages. On the 
other hand, urines containing fibrin in solution are likewise seen 
but rarely, and are characterized by the fact that fibrinous coagula 
separate out only on standing, when they usually cover the bottom 
of the vessel, but may at times change the entire bulk of urine into 
a gelatinous-looking mass. So far this condition has been observed 
only in cases of chyluria (which see). 

Nucleo-albumin. The question whether or not nucleo-albumin 
is a normal constituent of the urine is still a matter of dispute. 
Personal investigations have led the writer to the conclusion that 
with complicated methods and large amounts of urine — from 5 to 
25 liters — it is always possible to demonstrate its presence both 
under physiologic and pathologic conditions. With the usual tests 
and smaller amounts of urine, however, negative results only are 
obtained in strictly normal individuals. Trichloracetic acid, witli 
which Stewart claims to have obtained positive results in every 
one of the 150 normal urines which he examined, does not precipi- 
tate nucleo-albumin, according to the writer's experience, when this 
is present in normal amounts. A nucleo-albuminnria, recognizable 
by the available tests, does not exist uiidrr normal conditions. Even 
under pathologic conditions nucleo-albumin is by no means al way- 
found. Sarzin thus was unable to demonstrate its presence in 200 



394 CLINICAL DIAGNOSIS. 

cases which be examined in Senator's clinic. Citron arrived at 
similar results, and the writer, after having carefully examined 
several thousand uriues in this direction, obtained positive results 
in only a very small percentage of cases. Its presence always indi- 
cates an increased degree of desquamation in some portion of the 
urinary tract. It is essentially met with in diseases which directly 
or indirectly involve the integrity of the epithelial lining of the 
uriniferous tubules or of the bladder. 

It has thus been frequently found in cases of acute nephritis and 
associated with febrile albuminuria, although its presence even then 
is not constant. In chronic nephritis it is more frequently absent 
than present. In cases of renal hyperemia and cystitis the results are 
variable. In thirty-two icteric urines Obermayer obtained positive 
results without exception, and it appears that in leukaemia nucleo- 
albumin is also quite constantly present. During the administra- 
tion of pyrogallol, naphthol, corrosive sublimate, tar preparations, 
arsenic, etc., as well as in cases of poisoning with aniline and illu- 
minating gas, large amounts of the substance may be fonnd. 

According to the writer's experience, nucleo-albumin is quite fre- 
quently observed in cases of so-called functional albuminuria, and it 
is not at all uncommon to find that this is still present when serum- 
albumin and serum-globulin can no longer be demonstrated, even 
with the trichloracetic-acid test. Xucleo-albuminuria may thus 
exist independently of the presence of the more common forms of 
albumin. This observation has also been made by Strauss, who 
found nucleo-albumin only in several cases of cystitis, in one case 
of chronic interstital nephritis, and in one case of emphysema pul- 
monum with renal hyperemia. 

The existence of a htematogenic form of nucleo-albuminuria has 
thus far not been satisfactorily demonstrated. 

Histon. Quite recently Kolisch and Burion were able to demon- 
strate the presence of histon in the urine of a case of leukaemia, an 
albuminous body which was first dicovered by Kossel in the red 
blood-corpuscles of the goose, and which was shovrn to exist in the 
leucocytes of human blood in combination with the acid leuko- 
nuclein, constituting the so-called nucleo-histon of Lilienfeld. 
According to these observers, the substance was always present 
in their case. The method which they employed in testing for its 
presence was the following: 

The urine of twentv-four hours was first examined for albumin. 



THE URINE. 395 

and this removed, if present. It was then precipitated with 94 
per cent, alcohol, the precipitate washed with hot alcohol and dis- 
Bolved in boiling water. Upon cooling, the solution thus obtained 
was acidified with hydrochloric acid and allowed to stand for several 
hours. Duriug this time a cloudiness, referable to a large extent 
to uric acid, develops, which is filtered off, when the filtrate is pre- 
cipitated with ammonia. In addition to certain mineral constituents, 
histon, if present, is also thrown down. The precipitate is collected 
upon a small filter and washed with ammoniacal water until the 
washings no longer give the biuret reaction. It is then dissolved 
in dilute acetic acid and the solution tested with the biuret test; 
if this yields a positive result, and if coagulation occurs upon the 
application of heat, the coagulum being soluble in mineral acids, 
the presence of histon may be inferred. 

It is not clear in what manner the histonuria is produced; so 
much, however, seems certain, that it is not solely dependent upon 
the increased destruction of leucocytes. 

A histon-like body has also been found in acute peritonitis, follow- 
ing appendicitis, in croupous pneumonia, erysipelas, and scarlatina. 

Tests for Albumin. The recognition of the various albuminous 
bodies which may occur in the urine is based partly upon their 
direct precipitation and partly upon color-reactions when treated 
with certain reagents. 

The number of tests which have from time to time been suggested 
is very large; many of them, after a brief period of use, have been 
discarded as useless or uncertain, while others have been employed 
only occasionally and have not received the recognition which they 
deserved from the fact that simpler tests existed, that they did not 
possess sufficient delicacy, or that in some instances it was too great. 
In the following pages no attempt will be made to describe all of 
these tests, and attention will be directed only to those which are 
generally used and which clinical experience has proved to be of 
value, precedence being given to those which have been longest in 
use. While some of these are applicable for demonstrating the 
presence of more than one form of albumin, special tests will also 
be described whereby the various albumins may be individually 
recognized. 

In every case the urine should be carefully filtered, so as to free 
it from any morphologic constituents, etc., present. To this end it 
is generally sufficient to pass the urine through one or two layers 



396 



CLIXICAL DIAGXOSIS. 



Fig. 94. 



of Swedish filter-paper. Frequently, however, a clear specimen 
cannot be obtained in this manner; it is then advisable to shake 
the urine with magnesia usta, or to mix it with scrapings of filter- 
paper, when it is filtered as usual. 

Tests for Seroi-alboiix. The nitric-acid test. (Fig. 94.) 
The value of this test, properly applied, cannot be overestimated, 

as it is not only simple, but 
yields an amount of information 
that can otherwise only be 
gained with difficulty; informa- 
tion, moreover, which is valua- 
ble in many respects. Usually 
the student is advised to make 
use of a test-tube partially filled 
with urine, along the sides of 
which concentrated, chemically 
pure nitric acid is allowed to 
flow, so as to form a layer at 
the bottom of the tube, when in 
the presence of serum-albumin 
a distinct white cloud will ap- 
pear in the form of a ring at the 
zone of contact between the two 
liquids (Hellers test). The 
pictures thus obtained cannot 
be compared, however, with 
those seen when the apparently 
trivial change is made of using a conical glass of about 2 ounces 
capacity instead of the test-tube. About 20 c.c. of urine are placed 
in the glass, and 6 to 10 c.c. of nitric acid added by means of a 
pipette, which is carried to the bottom of the vessel, when the acid is 
slowly allowed to escape by diminishing the pressure of the finger 
upon the tube. When this is carefully done, as in Heller's test. 
the nitric acid forms a distinct zone beneath the urine. In the pres- 
ence of albumin the cloud referred to above will be seen, its extent 
and intensity varying with the amount of albumin present. (Plate 
X., Fig. 1.) If now the glass be allowed to stand for some time — 
and if small amounts be present, these only appear on standing — it 
will be observed that gradually the cloudiness extends upward, the 
upper border of the albumin-ring, with few exceptions, being at 




Xitric acid test. 



PLATE X. 



FIG. 2. 



FIG. A,. 









FIG. 1. 








FIG. 3. 




FIG. 5. 





THE URINE. 397 

first as well defined as the lower border, when the coagulated albu- 
min may be seen to rise into the supernatant liquid in the form of 
small, irregular columns. This appearance may possibly be refer- 
able to the partial decomposition of uric acid by means of nitric 
acid, nitrogen and carbon dioxide being set free, which, rising to 
the surface in the form of small bubbles, carry the nitric acid 
upward; this coming into contact with albumin in solution then 
causes the precipitation of the latter. An excess of uric acid, more- 
over, is indicated by the appearance, within five to ten minutes after 
the addition of the nitric acid, of a distinct ring in the clear urine 
about 1 to 2 cm. above the zone of contact, which is similar in 
appearance to that due to albumin. If this ring (Plate X., Figs. 
1. '2, and 3), which has been very appropriately compared to a holy 
wafer, does not appear within five to ten minutes, it may be assumed 
that the uric acid is present in diminished amount; on the other 
baud, it is possible to determine the degree of increase by the size 
of the ring, it being presupposed that the same quantities of urine 
and of the reagent are employed in every case. 

Should more than 25 grammes of urea be contained in a liter 
of the urine examined, an appearance like hoarfrost will be noted 
on the sides of the vessel, due to the formation of urea nitrate, while 
spangles of the same substance only appear in the presence of at 
least 45 grammes. Should 50 grammes or more of urea be con- 
tained in the liter, a dense mass of urea nitrate may be seen to 
separate out. 



DESCRIPTION TO PLATE X. 

Fig. 1 The nitric-acid test as applied to the urine : The light, colorless ring in 
the clear urine above shows a slight increase in the amount of uric acid ; the large 
white baud denotes a large amount of albumin, bordering upon a colored ring, 
referable partly to indican (blue) and partly to urorosein. 

Fig. 2. The nitric-acid test as applied to the urine : The light ring in the clear 
urine above denotes a slight increase in the amount of uric acid. The bluish-black 
band is referable to an enormous increase in the amount of indican. Taken from 
a case of ileus. 

Fig. 3. The nitric-acid test as applied to the urine : The broad, light band in 
the clear urine above is referable to an enormous increase in the amount of uric 
acid. Taken from a case of laparotomy. 

Fig. 4. The nitric-acid test as applied to the urine : The color play referable to 
the presence of bilirubin is shown in a diagrammatic manner 

FlG. 5. The nitric-acid test as applied to the urine : The colored ring is referable 
to the presence of normal urinary coloring matter. 



398 CLINICAL DIAGNOSIS. 

Biliary urine when treated with nitric acid containing a little 
nitrous acid shows the color-play referable to the action of nitric 
acid upon bilirubin (Plate X., Fig. 4), the production of the colors, 
yellow, green, blue, violet, and red, taking place from above 
downward, the green color being the most characteristic; in the 
absence of the latter the presence of biliary pigment may be posi- 
tively excluded. The presence of albumin is not at all objection- 
able, as the color-play takes place beneath the albuminous disk. 

In normal urine a transparent, colored ring is also obtained, pre- 
senting a peach-blossom red, the intensity of which, however, may 
vary from a faint rose to a pronounced brick color, referable to 
normal urinary pigment. (Plate X., Fig. 5.) In the presence of 
urobilin, on the other hand, this ring presents a distinct mahogany 
color. 

Indican is indicated by the appearance of a more or less violet 
ring (Plate X., Fig. 2) situated above that referable to the normal 
urinary pigment, its intensity varying with the amount present, 
from a light blue to a deep indigo -blue, which may color the entire 
urine when this is shaken. 

A cloud at the zone of contact of the two fluids may be referable 
not only to the presence of serum-albumin, but also of globulin and 
albumoses (propep tones), while a negative reaction will generally 
indicate the absence of these bodies. That the uric-acid ring will 
be mistaken for albumin is hardly likely, if it be recollected that 
this never first appears at the zone of contact of the two fluids, but 
always in the uppermost portion of the urine. It is true that urines 
are occasionally observed in which the separation of uric acid, 
always in the amorphous form, takes place so suddenly that within 
a minute or two the entire urinous portion of the mixture is com- 
pletely clouded, resembling the appearance presented by a highly 
albuminous urine. Such an excessive elimination of uric acid is 
quite uncommon, however, and it is to be remembered that with 
uric acid the cloudiness proceeds from above downward, and never 
from below upward, as is the case with albumin. Should any 
doubt be felt, it is only necessary to remove a few c.c. of this 
cloudy urine by means of a pipette and heat them gently in a test- 
tube, when the urine will clear up entirely if the precipitate be due 
to uric acid, while if caused by albumin it will remain or become 
still more intense. Should the precipitate caused by nitric acid 
consist of albumoses, this will also clear up entirely, to reappear on 



THE URINE. 399 

cooling, the fluid at the same time assuming a distinct yellow color. 
The occurrence of a distinctly yellow color in the urine, moreover, 
which is only partially cleared upon the application of heat, and he 
it remembered that a much higher temperature is necessary for the 
solution of a precipitate referable to albumoses than of one due to 
urates, will indicate the existence of a mixed albuminuria — /. e., 
the presence of coagulable albumin and albumoses. Xitric acid 
may also cause a precipitation of certain resinous bodies, such as 
those contained in turpentine, balsam of copaiba and tolu, etc. If 
any doubt be felt, the mixture should be shaken with alcohol, when 
the precipitate caused by these substances is at once dissolved. The 
mucinous body — nucleo-albumin — which is at times found in the 
urine, is also precipitated by nitric acid, but need not occupy our 
attention at this place. From what has been said it is manifest 
that the employment of the nitric-acid test in the manner indicated 
furnishes much valuable information, and the adoption of the 
method, as described, not only by hospital students, but by general 
practitioners as well, cannot be too strongly urged. 

Boiling-test. A few c.c. of urine are boiled in a test-tube and 
then treated with a few drops of concentrated nitric acid, no matter 
whether a precipitate has occurred upon boiling or not. If albu- 
min be present, this will separate out as a flaky precipitate, which 
consists of serum-albumin frequently mixed with serum-globulin. 
It is true that albuminous urines will generally yield a preciptate 
on boiling alone, but it must be remembered that unless the reac- 
tion be decidedly acid, a preciptation of normal calcium phosphate 
may occur owing to the fact that the reaction of the urine upon 
boiling becomes less acid, probably owing to an escape of the car- 
bonic acid held in solution. In urines presenting an alkaline or 
amphoteric reaction this is very frequently noted, and might give 
rise to confusion, as the precipitate due to calcium phosphate very 
closely resembles that due to albumin. Care must hence be taken 
to insure a distinctly acid reaction, which is best accomplished by 
the addition of nitric acid, when a precipitate referable to phos- 
phates is at once dissolved, while one due to albumin remains and 
may even become more marked. The quantity to be added should 
usually be equivalent to about 0.05 to 0.1 of the volume of the 
urine, and under no consideration should the acid be added before 
boiling, nor should the urine be boiled after its addition, as small 
amounts of albumin will otherwise be overlooked, owing to the fact 



400 CLINICAL DIAGNOSIS. 

that hot nitric acid dissolves the precipitate to a certain degree. If 
after the addition of the nitric acid the urine turns a distinct yellow, 
and if then upon cooling a white precipitate appears, the presence of 
albumoses may be inferred. Uric acid will probably never cause 
confusion, as this only separates out upon cooling, and then presents 
a dark-brown color. As in the case of the nitric-acid test, so also 
here, a precipitation of certain resins is noted at times, which may, 
however, be recognized by their solubility in alcohol. 

Should acetic acid be used instead of nitric acid, great care must 
be taken to avoid an excess, as otherwise the albumin will be dis- 
solved. As this danger diminishes the greater the quantity of salts 
contained in the urine, it is advisable to treat the urine first with 
a few drops of acetic acid until a distinctly acid reaction is obtained, 
and then to add one-sixth of its own volume of a saturated solution 
of sodium chloride, magnesium sulphate, or sodium sulphate, when 
upon boiling a precipitation of the albumin will take place. Car- 
ried out in this manner, the test is absolutely certain and will demon- 
strate even minimal amounts of albumin. 

The potassium f err oeyanide test. A few c.c. of urine are strongly 
acidified with acetic acid (sp. gr. 1.064) and treated with a few 
drops of a 10 per cent, solution of potassium ferrocyanide, when 
in the presence of but little albumin a faint turbidity, or, if much 
albumin be present, a flaky precipitate, is noted, which is best recog- 
nized by comparison with a tube containing some of the pure filtered 
urine, both tubes being held against a black background. Concen- 
trated urines should be previously diluted with water, as propep- 
tones, like serum-albumin and serum-globulin, which may be pre- 
cipitated in this manner, otherwise remain in solution. Here, also, 
as in the tests described, the presence of propeptones may be in- 
ferred if the precipitate disappears upon boiling, while a partial 
clearing up, on the other hand, indicates the presence of both 
albumoses and coagulable albumin. 

At times the addition of acetic acid by itself is followed by the 
appearance of a cloud in the urine, which may be due to urates or 
to urinary mucin (nucleo-albumin), as already mentioned. In such 
cases the urine should be refiltered and diluted with water and the 
test again applied. 

v. Jaksch advises the careful addition, by means of a pipette, of 
a few c.c. of fairly concentrated acetic acid to which a little potas- 
sium ferrocyanide has been added, when the albumin, as in Heller's 



THE URINE. 401 

test, is seen to form a ring at the surface of contact between the two 
fluids. Instead of potassium ferrocyanide, potassium platinocyanide 
may also be employed, and has the advantage that the test-solution 
is colorless. 

The trichloracetic-acid test. This test is undoubtedly the most 
delicate of those so far described, but not so delicate that a trace 
of albumin, or nucleo-albumin, as has been suggested by some, can 
be demonstrated in every urine. An experience based upon the 
examination of several thousand urines with this reagent warrants 
the author's speaking with a certain amount of confidence upon 
the subject. Very frequently it is possible with this method 
to demonstrate albumin in urines in which the more common 
tests yield negative results, but in which tube-casts may neverthe- 
less be found upon microscopic examination. The test is applied 
as follows: By means of a pipette, 1 or 2 c.c. of an aqueous solu- 
tion of the reagent (sp. gr. 1.147) are carried to the bottom of a 
test-tube containing the carefully filtered urine, so as to form a 
layer beneath the urine, when, in the presence of albumin, a white 
ring will be seen to form at the zone of contact between the two 
fluids, varying in intensity with the amount of albumin present. 
As far as the test for albumin is concerned, this reagent possesses 
an advantage over the nitric acid in that the colored rings, so often 
confusing to the inexperienced, are but rarely observed. Serum- 
albumin, serum-globulin, and albumoses are thus precipitated, the 
presence of the latter being recognized, as in the previous tests, by 
the fact that the precipitate disappears upon boiling, to reappear 
again upon cooling. A cloud, referable to uric acid, also appears if 
this be present in excessive amounts, but it is readily distinguished 
from that caused by albumin by the fact that it disappears upon the 
application of gentle heat. Furthermore, a previous dilution of the 
urine guards against this occurrence. 

Other tests have also been suggested for the detection of albumin 
in the urine, such as the metaphosphoric-acid test, the phenol, 
tannic-acid, and picric-acid tests, that with Tanret's reagent, phos- 
photungstic and phosphomolybdic acids, and quite recently Spieg- 
ler's reagent. 

Of these, only the picric-acid and Spiegler's tests will be consid- 
ered. 

Picric acid test. The picric-acid test is not applicable as a test 
for albumin as such, and is only mentioned in this connection be- 

26 



402 CLISICAL DIAGNOSIS. 

cause Esbach's quantitative method is based upon it. His reagent 
is composed of 10 grammes of picric acid and 20 grammes of crys- 
tallized citric acid, dissolved in a liter of distilled water. If to this 
solution albuminous urine be added, the mixture is rendered turbid, 
and after some time a sediment which consists not only of albumins, 
but also of uric acid, kreatinin, and other extractives, will form at 
the bottom of the tube. (See Quantitative determination of albumin.) 

Spiegler's test. Spiegler s reagent consists of 8 parts by weight of 
mercuric chloride, 4 parts of tartaric acid, and 200 parts of water, in 
which 20 parts of cane-sugar are further dissolved so as to increase 
the specific gravity of the reagent and permit of its being employed, 
like Heller's test, in even concentrated urines. One-third of a 
test-tube is filled with the reagent, and the urine carefully placed 
above this by allowing it to flow slowly down the side of the tube; 
in the presence of albumin a sharply defined white ring will be 
observed where the two liquids are in contact. Peptone gives no 
reaction, while albumoses are precipitated and may be recognized 
as indicated above. 

Special test jot serum-albumin. Should it be desired, for any 
reason, to demonstrate serum-albumin alone, the urine is rendered 
amphoteric or faintly alkaline with sodium hydrate, and then satu- 
rated with magnesium sulphate in substance, in order to remove 
any globulin. The filtrate is strongly acidified with acetic acid, 
when a flaky precipitate, appearing upon boiling, will indicate the 
presence of serum-albumin. 

Very often, as in the examination for sugar, it is necessary to 
remove any coagulable albumin that may be present, to which end 
the urine is rendered distinctly acid with acetic acid and boiled. 
An examination of the filtrate with potassium ferrocyanide, if the 
amount of acetic acid added was just sufficient, will then yield a 
negative result (see p. 404). 

Quantitative Estimation of Albumin. For the quantita- 
tive estimation of albumin a number of methods have been devised, 
which fact in itself is sufficient to indicate that the majority of these, 
at least, are unsatisfactory. 

Old method by boiling. If only comparative results are to be 
obtained, the old method of boiling a definite amount of urine, 
after the addition of acetic acid, and allowing the albumin to settle 
for twenty-four hours, may be employed. For this purpose Xeu- 
bauer suggests the use of glass tubes measuring one-half to three- 



THE URINE. 



403 



Fig. 95. 



quarters of an inch in diameter, closed at the lower end with a cork, 
into which the urine is poured. Ordinary test-tubes answer the 
purpose perfectly well, but care should be taken that the same quan- 
tity of urine be used in every case. These tubes may then be 
corked and kept for several days for comparison. Of course, the 
results obtained express only the relative amount of albumin present, 
and it should be remembered that the errors incurred may amount 
to as much as 30 or even 50 per cent., when compared with those 
obtained gravirnetrically, owing to the fact that sometimes the albu- 
min separates out in large flakes, and at other times in small flakes, 
and that the degree of precipitation is also influenced by the specific 
gravity of the supernatant urine. 

Volumetric method of Wassiliew. This method can be strongly 
recommended for the quantitative estimation of albumin, as it is 
both simple and accurate. 

Ten to twenty c.c. of urine, which are best diluted to 50 c.c. with 
distilled water, are treated with 2 drops of a 1 per cent, aqueous 
solution of true yellow and then titrated with a 25 per 
cent, solution of salicyl-sulphonic acid until a distinct 
brick-red color is obtained. The number of c.c. em- 
ployed multiplied by 0.01006 will then indicate the 
amount of albumin contained in the 10 or 20 c.c. of 
urine examined. If the urine be alkaline, it should 
first be slightly acidified with acetic acid. 

EsbacKs method. For clinical purposes, Esbach's 
method is the most convenient. As stated above, his 
reagent is composed of 10 grammes of picric acid and 
20 grammes of citric acid, dissolved in 1000 c.c. of dis- 
tilled water. Special tubes, termed albuminimeters 
(Fig. 95), are employed which bear two marks, one, U, 
indicating the point to which urine must be added, and 
one, R, the point to which the reagent is added. The 
lower portion of the tube up to U bears a scale reading 
from 1 to 7. The tube is filled to U with the filtered 
albuminous urine, and the reagent added until the point 
It is reached. The tube is then closed with a stopper, 
inverted twelve times, and set aside for twenty-four 
hours. At the expiration of this time serum-albumin, serum-globulin, 
and peptones, as well as uric acid and kreatinin, will have settled 
down, when the amount pro mille in grammes may be directly read 



Esbach's al- 
buminimeter. 



404 CLISICAL DIAGNOSIS. 

off from the scale. A few precautions must, however, be observed 
in order to obtain as accurate results as possible. The reaction of 
the urine should be acid, and if such be not the case acetic acid is 
added. Its specific gravity should, furthermore; not exceed 1.006 
or 1.008, the proper density being obtained by diluting with water. 
The temperature also appears to play an important rule, the reading 
generally being higher with a low than with a more elevated tem- 
perature. 15° C. being best adapted to our purposes. 

~ u differential density method. More accurate results may be 
obtained with the following method, which is based upon the 
diminution in the specific gravity of the urine after the removal of 
all albumin, and its comparison with the specific gravity observed 
before. To this end the urine is treated with a sufficient amount 
of acetic acid to insure a complete precipitation of the albumin (see 
below), when its specific gravity is noted. It is then brought to 
the boiling-point, care being taken to guard against evaporation by 
placing the urine in an ordinary medicine-bottle, closing this with a 
rubber stopper that has been previously boiled in a sodium hydrate 
solution and washed until free from an alkaline reaction, the stopper 
being tightly fastened with a cord or wire. Thus prepared, the 
bottle is kept in boiling water for ten to fifteen minutes, the urine 
filtered upon cooling, evaporation being again carefully guarded 
against by filtering into a bottle through a funnel which has been 
passed through a closely fitting stopper, the funnel being kept cov- 
ered by a plate of glass, when the specific gravity is again deter- 
mined, it being best in both cases to use a pyknometer. The 
decrease in the specific gravity, multiplied by 400. will indicate the 
number of grammes of albumin contained in 100 c.c. of urine. 

1 :imetric method. If special accuracy be required, the amount 
of albumin must be determined gravimetrically as follows: A cer- 
tain amount of urine, after having been acidified with acetic acid to 
such a degree as to insure a complete separation of all albumin, is 
boiled; the albumin is then filtered off. dried, and weighed. For 
this purpose, 500 to 1000 c.c. of carefully filtered urine should be 
available. A specimen of this, if already acid, is placed in a test- 
tube in boiling water until coagulation takes place, when it is fur- 
ther heated over the free flame and filtered. The filtrate is then 
tested with acetic acid and potassium ferrocyanide. Should no 
albumin be thus demonstrable, the entire amount of urine is treated 
in the same manner and requires no further addition of acetic acid. 



THE URINE. 405 

If, however, the test yields a positive result, it is apparent that the 
urine was not sufficiently acid. The entire volume is then treated 
with a 30 to 50 per cent, solution of acetic acid, drop by drop, the 
mixture being thoroughly stirred and specimens being tested from 
time to time, as described. When, finally, the urine remains clear 
or shows only a faint turbidity, 100 c.c. or less, according to the 
amount of albumin present, are first heated in boiling water until 
the albumin begins to separate out in flakes, and then carefully 
brought to the boiling-point over the free flame. The supernatant 
urine is now decanted off through a filter, dried at 120° to 130° C, 
and accurately weighed, when the whole amount of the precipitate 
is itself brought upon the filter. Any albumin remaiui ng in the 
beaker is detached from its sides by means of a small glass rod, 
tipped with a piece of rubber-tubing and collected by the aid of hot 
water, with which the entire precipitate is now thoroughly washed, 
until the washings no longer become turbid when treated with a 
drop of nitric acid and silver nitrate; in other words, until the 
chlorides have been completely removed. The precipitate is fur- 
ther washed with alcohol and finally with ether to remove any fats 
that may be present, when it is dried at 120° to 130° C. until a 
constant weight is reached. If still greater accuracy be required, 
the dried and weighed precipitate must now be incinerated to deter- 
mine the amount of mineral ash in combination with the albumin, 
which is then deducted from the previous weight. The best results 
are obtained if not more than 2 to 0.3 gramme of albumin is con- 
tained in the amount of urine employed, so that a smaller quantity 
than 100 c.c. should be used if a previous test with Esbach's albu- 
minimeter shows a higher percentage. 

A glass-wool filter insures a more rapid process of drying — twenty- 
four to thirty hours; but care must then be had that this is properly 
prepared, so as to guard against a loss of the wool while washing. 

Test for Serum-globulin and its Quantitative Estima- 
tion. To test for serum-globulin the urine is rendered alkaline by 
the addition of ammonium hydrate, any phosphates that may thus 
be thrown down being filtered off on standing. The urine is then 
treated with an equal volume of a saturated solution of ammonium 
sulphate, when the occurrence of a precipitate will indicate the pres- 
ence of the globulin. Ammonium urate, which may likewise sepa- 
rate out, can always be recognized by its color. 

According to Paton, the following test may also be employed: The 



406 CLINICAL DIAGNOSIS. 

urine after having been rendered alkaline with sodium hydrate — 
any phosphates which may separate out being filtered off — is care- 
fully poured down the side of a test-tube containing a saturated 
solution of sodium sulphate so as to form a layer above this, when 
in the presence of serum -globulin a white ring will appear at the 
zone of contact. 

If a quantitative estimation of the globulin is to be made, the pre- 
cipitate thus obtained, after about one hour's standing, is collected 
on a dried and weighed filter and washed thoroughly with a one- 
half saturated solution of ammonium sulphate until a specimen of 
the washings treated with acetic acid and potassium ferrocyanide 
no longer gives a precipitate. It is then treated as directed in the 
method employed for the quantitative estimation of serum-albumin. 

Tests foe Albumoses. It has been pointed out that the albu- 
moses are precipitated in the ordinary tests for serum-albumin, and 
that a precipitate referable to these bodies will clear up upon the 
application of heat, to reappear again upon cooling, and that in the 
presence of nitric acid the fiuid will assume a deep yellow color. 
If, however, coagulable albumin be also present, which is usually 
the case, this should first be removed by strongly acidifying the 
urine with acetic acid, adding an equal amount of a saturated solu- 
tion of sodium chloride and boiling. Should albumoses be present, 
these will separate out in the filtrate upon cooling. If, furthermore, 
the hot filtrate be rendered alkaline with sodium hydrate, a red color 
(biuret-reaction) will result upon the addition of a very dilute solu- 
tion of copper sulphate, added drop by drop. When boiled with 
Millon's reagent a red color is also obtained. This reagent is pre- 
pared by dissolving 1 part of mercury in 2 parts of nitric acid of a 
specific gravity of 1.42 and diluting with 2 volumes of water. 

Test for Peptones. That peptones in the sense of Kiiline do 
not occur either in normal or pathologic urines has already been 
pointed out, and the method to be described has therefore only 
reference to peptone in the older sense of the word. Hof meister' s 
method is so tedious and time-consuming that the author has sub- 
stituted Salkowski's modification, which is both accurate and simple, 
so much so in fact that its general adoption in the clinical labora- 
tory can be strongly recommended. 

Fifty c.c. of urine are acidified in a beaker with 5 c.c. of hydro- 
chloric acid, and precipitated with phosphotungstic acid, the mix- 
ture being heated over the free flame, when in a few minutes the 



THE URINE. 407 

precipitate will form a resinous mass which closely adheres to the 
bottom of the vessel. The supernatant fluid is decanted off, and 
the mass at the bottom, which now becomes granular, washed twice 
with distilled water, which is likewise removed by decantation. 
The precipitate is then covered with about 8 c.c. of distilled water, 
and treated with 0.5 c.c. of a sodium hydrate solution (sp. gr. 1.16). 
Upon shaking the beaker the mass will dissolve, the solution as- 
suming a dark-blue color. This is heated on the free flame until 
the blue color turns to a dirty, grayish-yellow; the solution at the 
same time becomes turbid, but at times may turn yellow and re- 
main clear. This discoloration may be hastened by the further 
addition of a few drops of sodium hydrate solution. As soon as 
this point has been reached, some of the liquid is placed in a test- 
tube, allowed to cool, and then treated with a very dilute solution 
of copper sulphate (1 to 2 per cent.), drop by drop, when in the pres- 
ence of peptones the solution assumes a bright-red color, which may 
be brought out still more strongly if the specimen is now filtered. 
If albumin or much mucin be present, these bodies must first be 
removed (see p. 404 and below); but the quantity of urine employed 
is so small that the mucin can be usually disregarded. With this 
method, w r hich occupies only about five minutes, 0.015 gramme of 
peptones pro 100 c.c. may be demonstrated without difficulty. 

Salkowski has recently pointed out that urines which are very 
rich in urobilin, as in pneumonia, may give rise to the biuret-reac- 
tion even when albumoses are absent. The coloring-matter, it is 
true, may be removed entirely by precipitation with acetate or sub- 
acetate of lead, but a portion of the albumoses unfortunately is 
also carried down, and the substance may thus escape detection 
when present in only small amounts. He hence suggests that 
smaller quantities of urine, such as 10 c.c, be employed in the 
test. The reaction is then not so well marked, but the results are 
more reliable. 

Tests for (Mucin) Nucleo-albumin. The carefully filtered 
urine is treated in a test-tube drop by drop with an excess of con- 
centrated acetic acid, when the occurrence of a turbidity will indi- 
cate the presence of nucleo-albumin. 

If the urine contain albumin, this must first be removed, simple 
boiling being sufficient. Dilution of the urine (1 part to 3 of water) 
should also be practised when any doubt is felt, as urates will then 
not interfere with the reaction, nor will the urinary salts, if these 



408 CLINICAL DIAGNOSIS. 

be present in large amounts, be so apt to exert a solvent action 
upon the mucin. 

Ott ? s test may also be advantageously employed. To this end a 
few c.c. of urine are treated with an equal volume of a saturated 
solution of common salt, when Almen's solution, consisting of 5 
grammes of tannic acid, 10 c.c. of a 25 per cent, solution of acetic 
acid, and 240 c.c. of 40 to 50 per cent, alcohol, is slowly added. 
In the presence of nucleo-albumin a precipitate develops at once. 

Xucleo-albumin is characterized by its insolubility in acetic acid, 
in the fact that it is preciptated by magnesium sulphate and that it 
does not give rise to the formation of a reducing substance when 
boiled with dilute acids. It is thus readily distinguished from 
globulin and true mucin, with which it has frequently been con- 
founded. Globulin precipitates are easily soluble in acetic acid, 
and mucin, when boiled with acids, gives rise to the formation of 
a reducing substance. 

In order to remove nucleo-albumin from the urine this is treated 
with neutral acetate of lead, an excess of the reagent being care- 
fully avoided. If it is desired to test for peptones, the filtrate is 
then treated with hydrochloric acid and the process continued as 
described above. 

Tests for Hjemoglobix. The diagnosis of hemoglobinuria is 
based upon the demonstration of hemoglobin, viz., methemoglobin 
in the urine in solution, in the absence of red corpuscles, or at least 
in the presence of only a very small number, so that an examination 
in the latter direction also is an important factor. 

Bloody urine is generally turbid and may vary in color from 
bright-red to almost black. 

Oxyhemoglobin, as such, can only be recognized by the spectro- 
scope, giving rise to the appearance of two bands of absorption, 
situated between D and E, as described in the chapter on the Blood. 

The urine to be examined spectroscopically should be rendered 
feebly acid by means of acetic acid, and placed before the open slit 
of the spectroscope in a test-tube, beaker, or similar vessel, when 
the two bands of oxyhemoglobin will be seen either at once or 
upon carefully diluting with distilled water. If ammonium sul- 
phide be now added, the spectrum of reduced hemoglobin will be 
obtained. It must be remembered, however, that more commonly 
the spectrum of methemoglobin is seen in cases of hemoglobinuria. 

The following tests, which will also indicate the presence of blood 



THE URINE. 409 

coloring-matter, cannot be employed to decide the nature of the pig- 
ment present, as rnetlmemoglobin and oxyhemoglobin will both react 
in the same manner. 

Heller's test. Some of the urine to be examined is boiled in a 
test-tube with caustic potash, when in the presence of blood color- 
ing-matter the precipitate, which consists of basic phosphates, will 
present a bright-red color. At times, when the urine contains a 
large amount of coloring-matter (bile-pigment, etc.), it may be dif- 
ficult to appreciate the color of this sediment; in this case it should 
be filtered off and dissolved in acetic acid, when if blood-pigment 
be present the solution becomes red, and the color vanishes gradu- 
ally upon exposure to the air (v. Jaksch). Instead of this test, 
the following one may also be advantageously employed, but, in 
the author's experience, it does not surpass in delicacy that just 
described. 

The guaiaeum test. A mixture of equal parts of tincture of 
gnaiacum and oil of turpentine, which has been ozonized by ex- 
posure to the air, is allowed to flow carefully along the side of a 
test-tube upon the urine to be examined in such a manner as to 
form a distinct layer above the urine, when in the presence of 
blood-pigment a white ring which gradually turns to blue will be 
seen to form at the surface of contact. 

Test for Fibrin. Fibrin usually occurs in the urine in the 
form of distinct clots, the nature of which may be determined by 
thoroughly washing them with water, when they are dissolved by 
boiling in a 1 per cent, solution of soda or a 5 per cent, solution of 
hydrochloric acid. Upon cooling, this solution is then tested as for 
serum-albumin. 

Test for histon. (See p. 394.) 

Carbohydrates. 

The carbohydrates which may occur in the urine are glucose, 
lactose, maltose, dextrin, levulose, inosit, and animal gum. Of 
these, glucose alone will be considered in detail in the following 
pages, as being the only one of clinical interest. 

Glucose. The question whether sugar — i. e., glucose — can occur 
in the urine under normal conditions has been as much discussed 
as the existence of a physiologic albuminuria, and may now be 
definitely answered in the affirmative. Kiilz and Moscatelli, it is 
true, were unable to demonstrate its presence even in such large 



410 CLINICAL DIAGNOSIS. 

quantities of urine as 200 liters; the methods employed by these 
observers, however, were not sufficiently accurate, and more recent 
investigations in Baumann's laboratory leave no doubt as to the 
existence of a physiologic glycosuria. A trace of glucose is of no 
clinical significance, being demonstrable only with the most deli- 
cate methods; with the tests usually employed a normal urine is 
apparently free from sugar. Nevertheless, there appears to exist a 
limit to the assimilation of glucose on the part of the body-economy, 
the over-stepping of which leads to glycosuria, termed by Claude 
Bernard " glycosurie alimentaire." 

The question now arises, Where does this limit lie ? Notwith- 
standing numerous experiments made in this direction, a definite 
answer cannot as yet be given, for, while some observers have 
demonstrated that the ingestion of 200 to 250 grammes of sugar 
does not lead to glycosuria, sugar has been found by others after 
the ingestion of only 100 grammes, and Helfereich even claims to 
have found sugar in the urine of individuals living upon an exclu- 
sively vegetable diet. 

v. Jaksch states that glycosuria following the ingestion of so small 
an amount as 100 grammes of chemically pure glucose must be 
considered as pathologic, an observation with which those of the 
author accord perfectly. A pathologic digestive glycosuria follow- 
ing the ingestion of from 100 to 150 grammes of glucose has been 
observed by Kraus, Ludwig, and Chvostek in cases of atrophic 
hepatic cirrhosis, pancreatic cysts, diabetes insipidus, Basedow's 
disease, and in one case of tachycardia, v. Jaksch, on the other 
hand, was unable to find sugar, under the same conditions, in the 
urine of two cases of hyperemia of the liver, one case of amyloid 
degeneration, and four cases of hepatic cirrhosis, of which two were 
of the atrophic and two of the hypertrophic variety. Referring to 
the contradictory results thus obtained, he regards these as acci- 
dental, and thinks it not at all improbable that a more satisfactory 
classification of hepatic diseases than that now existing could be 
made on the basis of an artificially produced digestive glycosuria. 
Negative results were reached in cases of leukaemia, anaemia, neph- 
ritis, and tuberculosis; of nervous diseases, in minor chorea, tabes, 
multiple sclerosis, progressive paralysis, hemiplegia, and cerebral 
tumors; while mere traces were found in a case of sciatica associ- 
ated with fatty degeneration of all organs, in one case of morphine- 
poisoning, and in one of renal tumor. Amounts of glucose large 



THE URINE. 411 

enough to be quantitatively determined were observed following 
the ingestion of lOO grammes in one case of cerebral atrophy simu- 
lating tumor and associated with renal cirrhosis, in one case of 
glioma of the corpus callosum, in one of chronic hydrocephalus, in 
one of cerebral syphilis, and in one of cerebral embolism. Definite 
conclusions cannot, of course, be drawn from so small a number 
of observations. It would appear, however, that diffuse cerebral 
lesions referable to alcohol and syphilis are more likely to give rise 
to digestive glvcosuria than more localized lesions. 

A digestive glycosuria has also been observed in febrile diseases, 
such as pneumonia, typhoid fever, acute articular rheumatism, scar- 
latina, tonsillitis, etc. The amount of sugar which is found usually 
varies from 0.5 to 3 per cent.; larger amounts may, however, also 
be encountered, and one case is on record in which 8 per cent, were 
present. 

The same is observed quite frequently during pregnancy, and in 
one case recorded by Lanz 29.6 grammes of glucose were found 
after the administration of 100 grammes. Such figures, however, 
are rare, and as a general rule less than 3 grammes are found. 
After confinement the power of assimilation for glucose no longer 
appears to be subnormal. Finally, it should be mentioned that in 
diabetes mellitus the sugar may also at times disappear from the 
urine, its elimination being replaced, as it were, by an excessive 
excretion of uric acid or phosphates. In such cases a glycosuria 
may be produced with ease by the ingestion of 100 grammes of 
glucose, a point which may be of considerable diagnostic value. 
It is also important to note that the exhibition of such amounts 
of sugar in true diabetes will cause an increased elimination, while 
this does not appear to occur in the other forms of glycosuria. 

Aside from the digestive form, just considered, which may be 
produced in any healthy individual by an over-indulgence in sugars 
and starches, a transitory glycosuria, not artificially produced, is 
met with under various conditions. A transitory glycosuria, 
apparently of central origin, is thus noted in connection with 
lesions affecting the central as well as the peripheral nervous 
system, such as tumors and hemorrhages at the base of the brain, 
lesions of the floor of the fourth ventricle, cerebral and spinal 
meningitis, concussion of the brain, fracture of the cervical verte- 
brae, tetanus, sciatica; following epileptic, hystero-epileptic, and 
apopletic seizures, mental shock produced by railroad accidents, 



412 CLINICAL DIAGNOSIS. 

(traumatic neuroses), etc., mental strain and worry, fatigue, and 
anxiety. Glycosuria following epileptic and apopletic attacks, 
however, does not appear to be so common as is generally believed. 
v. Jakseh was unable to demonstrate the presence of sugar in 50 
recent cases of hemiplegia, and the author has reached only nega- 
tive results in a large number of cases of epilepsy, with urines 
voided within the first few hours following the seizure. 

Siegmund noted a transitory glycosuria in 52.38 per cent, of 
general paretics, in ~ A per cent, of epileptics, and in 3.77 per cent. 
of dementia cases, while it was not observed in any other mental 
diseases. 

It is a well-known fact that Claude Bernard experimentally pro- 
duced a transitory glycosuria by puncturing a certain spot in the 
floor of the fourth ventricle, the supposed origin of the hepatic 
vasomotor nerves, and it is not improbable that this neurotic form 
of glycosuria is due to some direct or reflex influence affecting that 
portion of the medulla. 

The transitory glycosuria which is occasionally observed, par- 
ticularly during convalescence, in acute febrile diseases, such as 
typhoid fever, scarlatina, measles, cholera, diphtheria, influenza, and 
especially malaria, may possibly be referable to the action of 
ptomains or leukomains upon this centre, and Seegen reports five 
cases of malaria with :; diabetes" in which both conditions disap- 
peared under the administration of quinine. 

A glycosuria of toxic origin has been noted in cases of poisoning 
with curare, chloral hydrate, sulphuric acid, arsenic, alcohol, carbon 
monoxide, morphine, etc., and even after simple transfusion of nor- 
mal salt-solution into the blood. Phloridzin, a glucoside obtained 
from the bark of the root of the apple tree, will likewise cause 
sugar to appear in the urine, the glycosuria produced, however, 
being temporary and ceasing with the withdrawal of the drug. 

The occurrence of a transitory glycosuria under the conditions 
above mentioned, which, moreover, may be met with in almost any 
disease, while interesting from a theoretical standpoint, must, in 
the majority of instances, be regarded as a medical curiosity only, 
it being but rarely possible to draw either diagnostic, prognostic, 
or therapeutic conclusions from its existence. 

A persistent j "orm of glycosuria is noted in connection with certain 
lesions of the brain, especially those affecting the floor of the fourth 
ventricle, and is at times of considerable diagnostic value. 



THE URINE. 413 

A continuous elimination of sugar is noted principally in the com- 
plex of symptoms to which the term diabetes mell.itus has been 
applied, and it is this condition to which the greatest practical 
and theoretical interest attaches. 

Diabetes mellitus is essentially a persistent form of glycosuria, 
associated with the occurrence of a more or less intense polyuria and 
a greatly increased elimination of all the metabolic products nor- 
mally found in the urine, with the exception of uric acid, which is 
usually present in diminished amount. In the more advanced 
cases acetonuria, lipuria, and lipaciduria may also exist. Diabetes, 
however, is not a persistent form of glycosuria in an absolute sense 
of the word, since times may occur in the course of the disease when 
glucose cannot be demonstrated in the urine. 

The quantity of sugar excreted may be enormous, and 180 to 
360 grammes pro die may be quite frequently observed; but, as 
stated above, this quantity may diminish to zero under various 
conditions, such as the occurrence of intercurrent diseases, but 
often also without any apparent cause, and not infrequently in 
the condition which has been termed diabetic coma. Some cases 
are also at times observed in which, from beginning to end, mere 
traces are eliminated, the total amount of sugar not exceeding a few 
grammes, while the course of the disease rapidly tends toward a 
fatal termination, so that the severity of the pathologic process cannot 
be measured by the amount of sugar eliminated. A few years ago 
the author had occasion to observe a diabetic patient in whom for 
months a daily examination of the urine never revealed the pres- 
ence of more than 5 to 10 grammes of sugar per diem, and where 
death occurred after eighteen months. 

At the same time it should be remembered that diabetes cannot 
be excluded by one or even more negative urinary examinations, and 
the value of repeating such examinations three or four hours after 
the exhibition of 100 grammes of glucose, as indicated, cannot be 
too strongly insisted upon. 

Clinicians are in the habit of determining the severity of a case, 
to a certain extent at least, by the condition of the urine under a 
diet free from starches and sugars, generally regarding those cases 
as the more serious in which the glycosuria does not disappear under 
a diet of this character, a more favorable prognosis being given if 
the sugar disappears. It should be remembered, however, that 
there are numerous exceptions to this rule which may hold good in 



414 CLINICAL DIAGNOSIS. 

many instances, and that a light case — i. e. t one in which the sugar 
has disappeared under appropriate dietetic treatment — mar sud- 
denly exhibit symptoms seen only in the most severe forms, and 
succumb to one of the numerous intercurrent maladies, while 
apparently severe cases may suddenly assume the more benign type. 

It may not be out of place in this connection to say a few words 
■ ggaiding the specific gravity of the urine. TVhile usually very 
high, varying between 1.030 aud 1.060. as pointed out in the 
chapter on Specific Gravity, comparatively low figures are noted 
at times, such as 1.012, corresponding to a quantity of urine not 
-xoeeding 1000 c.c, and implying, of course, a greatly diminished 
elimination of solids. This is especially marked in those cases 
described by Hirsehf'eld. in which, as pointed out in the chapter 
on Urea, the resorption of nitrogenous material from the digestive 
tract is below par. Polyuria, a fairly constant symptom of the 
more common types of diabetes mellitus, is much less pronounced 
in Hirschf eld's form, and may be altogether absent, although it 
is true that this may occur in ordinary diabetes also. 

The simultaneous occurrence of glycosuria, acetonuria, lipuria, and 
lipaciduria | which see is probably always indicative of true diabetes. 

It is. of course, impossible to enter here into a detailed considera- 
tion of the origin of diabetes. Suffice it to say that a persistent 
glycosuria, aside from nervous influences, may be referable, on the 
one hand, to an inability on the part of the liver to transform into 
glycogen all of the sugar which is carried to this organ, or, on the 
other hand, to an inability on the part of the muscular system of 
the body to utilize all the sugar sent to it by the liver, which may 
have performed its work properly. Accordingly, we may distin- 
guish between a hepatogenic and a myogenic diabetes. As a matter 
of fact, cases are seen, usually belonging to the milder form of 
diabetes, in which the sugar may be temporarily caused to disap- 
pear from the urine by muscular exercise, a point which, bearing 
in mind the deleterious effect which a continuous excessive elimina- 
tion of solids exerts upon the kidneys, is certainly of great thera- 
peutic interest. On the other hand, again, cases are seen, and 
unfortunately only too frequently, in which, notwithstanding a 
total abstinence from carbohydrates and a free indulgence in mus- 
cular exercise, the sugar does not disappear from the urine. In 
lennissible to speak of a hepatogenic combined with 
a mrocrenic diabetes. 



THE URINE. 415 

Within recent years it has been shown that pancreatic disease is 
frequently associated with diabetes, and while the number of cases 
in which no pancreatic lesions were discovered is still too large to 
warrant the conclusion that disease of this organ is invariably asso- 
ciated with glycosuria, it must still be admitted that lesions of the 
pancreas are the more frequently met with in diabetes the more 
closely the organ is examined. It appears to be certain that 
diabetes may be produced by pancreatic disease. As to the man- 
ner, however, in which such a result can occur we are as yet in 
profound ignorance. 

Hirschfeld pointed out the fact that, while in the majority of 
diabetic patients the proteid food ingested is quite satisfactorily 
utilized, the assimilation of albumin and fats is very much below 
par in others, and particularly so in cases of diabetes associated 
with pancreatic disease. (See also Urea.) As yet, observations 
in this direction are scanty, so that a definite opinion cannot be 
expressed regarding the utility in diagnosis of investigations similar 
to those of Hirschfeld. The author had occasion to observe a 
diabetic patient for some length of time, in whom, notwithstanding 
that conclusions were reached similar to those of Hirschfeld, the 
existence of pancreatic disease could not be determined post mortem. 

Whether or not a renal and a thyroigenic diabetes also exists, as 
has recently been suggested, must still remain an open question. 

Tests for Sugar. The tests for sugar usually employed in the 
clinical laboratory depend upon the following properties of sugar: 

1. It acts as a reducing agent upon certain metallic oxides, such 
as copper and bismuth, in the presence of alkalies (Fehling's, 
Trommer's, Bottger's, and Ny lander's tests). 

2. In the presence of yeast (saccharomyces cerevisise) it under- 
goes fermentation, with the formation of alcohol, carbonic acid, 
succinic acid, glycerine, and a number of other bodies, such as 
amy] alcohol, etc. (fermentation test). 

3. With phenylhydrazin sugar forms an insoluble crystalline 
compound — phenylglucosazon. 

4. Solutions of glucose turn the plane of polarized light to the 
right, from which property glucose has also received the name 
dextrose. 

In every case the urine should first be tested for the presence of 
albumin, which should be removed by boiling. 

Trommer's test. A few c.c. of urine are strongly alkalinized in 



416 CLINICAL DIAGNOSIS. 

a test-tube with sodium hydrate solution, and then treated with a 5 
per cent, solution of sulphate of copper, added drop by drop, until 
the eiiprie oxide formed is no longer dissolved. The mixture is 
carefully heat?d, when in the presence of sugar a yellow precipitate 
of cuprous hydroxide is formed, which will gradually settle to the 
bottom as a red sediment of cuprous oxide. 

It is important to note that while sugar, unless present in mere 
traces, can readily be detected in this manner, other substances are 
or may be present in the urine, such as uric acid, kreatin and krea- 
tinin, allantoin. nucleo-albumin. milk-sugar, pyroca tec-bin. hydro- 
chinon, and bile-pigment, which may likewise redu:e cnpric oxide. 
Following the ingestion of benzoic acid, salicylic acid, glycerine, 
chloral, sulphonal. etc.. reducing substances also appear in the urine. 
These may. it is true, be generally disregarded, if care be taken not 
to boil the urine after the addition of the copper sulphate, as the 
precipitation of cuprous oxide in the presence of sugar takes place 
before this point is reached, and the result should be regarded only 
as positive if precipitation occurs in this manner. Unfortunately. 
however, the test, when thus applied, yields negative results. 
or results which are doubtful if mere traces only of sugar are 
present, so that it cannot be utilized, as a rule, in the study of 
transitory or digestive glycosuria. 

Fehlirufs test. This is a modification of the test just described. 
and can only be recommended with the same restrictions. 

Two solutions are employed, which must be kept in separate 
bottles, the one containing 34.64 grammes of crystallized copper 
sulphate dissolved in 500 c.c. of distilled water, and the other 173 
grammes of the tartrate of potassium and sodium and 125 grammes 
of potassium hydrate dissolved in 500 c.c. of distilled water. Equal 
parts of these two solutions, mixed in a test-tube and diluted with 
four times as much water, are boiled and a small amount of urine 
is added. In the presence of sugar a precipitate of the yellow 
hydroxide of copper or of red cuprous oxide will be produced, 
care being taken only to vio.rm. but not to boil the solution offer the 
addition of the uri 

Not infrequently it will be observed that upon standing, when 
no precipitation has occurred previously, the blue color of the 
mixture changes to an emerald-green, the solution at the same 
time becoming turbid. Such a phenomenon should not be re- 
ferred to the presence of sugar, it being in all probability due to 



THE URINE. 417 

the action of other reducing substances, such as those mentioned 
above. 

Bbltgcr's test with Nylander's modification. A few c.c. of urine 
are treated in the proportion of 11 : 1 with Almen's solution. This 
is prepared bv dissolving 4 grammes of the tartrate of potassium 
and sodium, 2 grammes of the subnitrate of bismuth, and 10 grammes 
of sodium hydrate in 90 c.c. of water, heating the solution to the 
boiling-point and filtering upon cooling, when it should be kept in 
a colored-glass bottle. The mixture of urine and Almen's fluid is 
thoroughly boiled, when in the presence of sugar a grayish, dark- 
brown, and finally a black precipitate, consisting of bismuthous 
oxide, Bi0 2 , or of metallic bismuth, is obtained. Albumin, if 
present, must first be removed, as owing to the sulphur contained 
in the albuminous molecule alkaline sulphides could be formed 
upon boiling, and acting upon the bismuth give rise to the forma- 
tion of black sulphide of bismuth, which may be mistaken for 
metallic bismuth. Rhubarb-pigment, as well as melanin and 
melanogen (which see), and free sulphuretted hydrogen must also 
be absent, as misleading results will otherwise be obtained. 

Xylander's test, as that of Trommer and Fehling, is, however, 
not without objections, as a partial reduction of the subnitrate of 
bismuth may also be produced by other substances, such as kairin, 
tincture of eucalyptus, turpentine, and large doses of quinine. The 
author observed a urine in which Fehling' s test yielded a positive 
result, and in which a blackish discoloration was observed with 
Nylander's test, but in which the fermentation-test failed com- 
pletely. The substance producing these results was glycosuria acid. 

Fermentation-test. A small piece of ordinary compressed yeast 
is shaken with some of the suspected urine and a test-tube filled 
with the mixture, to which some mercury is added. The tube is 
then iu verted into a vessel containing mercury and allowed to stand 
in a warm place (22°-28° C). If sugar be present, fermentation 
will occur in the course of twelve hours, and the carbon dioxide 
formed rise to the top of the tube, gradually expelling more and 
more of the urine or mercury, as the amount of the gas increases. 
It is easy to demonstrate that the gas thus formed is actually carbon 
dioxide by introducing a small piece of caustic soda into the urine, 
when, owing to absorption of the carbon dioxide, the liquid will 
again rise in the tube. Very convenient for this purpose also are 
the saccharimetric tubes of Einhorn (Fig. 96), which are employed 

27 



418 



CLINICAL DIAGNOSIS. 



as just described, a little mercury being poured into the bent limb 
to guard against an escape of gas. As the yeast itself, however, 
may give rise to the formation of a little gas in the absence of 
sugar, it will always be well to make a control-test with normal 
urine; i. e., to prepare a similar tube with normal urine mixed 
with yeast, and to allow this to stand at the same temperature. 
If a positive result be thus obtained, there can be no doubt as to 
the presence of a fermentable substance in the urine, which may 



Fig. 96. 




Einhorn's saccharimeter. 



not be glucose, however, as other carbohydrates, such as lactose, 
maltose, and levulose, will likewise undergo fermentation. Still, 
if large amounts of gas be obtained and if Trommels test also 
yields a positive result, it will be fairly safe to regard the substance 
present as glucose. 

Phenylhydrazin test. Six to eight c.c. of urine are treated with 
two pinches of phenylhydrazin hydrochlorate and 3 parts of acetate 
of sodium, and warmed until the salts have been dissolved, a little 
water being added if necessary. The tube is then placed in boiling 
water for twenty to thirty minutes, and then suddenly plunged into 
cold water. If sugar be present in moderate amounts, a bright 



PLATE XI. 




Phenyl-Glueosazon Crystals obtained from a Diabetic Urine. 



THE URINE. 419 

yellow crystalline deposit will at once be thrown down, and partly 
adhere to the sides of the tube. But even in the presence of 

more traces a careful microscopic examination will reveal the pres- 
ence of crystals of phenylglucosazon. These are highly character- 
istic (Plate XL), and cannot be mistaken for any other substance. 
They are seen singly or arranged in bundles and sheaves, composed 
of very delicate bright-yellow needles which are insoluble in water. 

This test, properly applied, is undoubtedly nut only the most deli- 
cate, but at the same time the most reliable, as no other substances 
which may be present in the urine, excepting maltose and certain 
pentoses, will give rise to the formation of an osazon. Hence, when- 
ever any doubt is felt as to the nature of a substance reacting in a 
positive manner with the reagents described above, recourse should 
be had to this test. It has been stated that maltose forms an ex- 
ception ; this, however, will never become embarrassing, as the 
microscopic appearance of maltosazon crystals differs from that of 
the phenylglucosazon. The melting-point of phenylglucosazon, 205° 
C, moreover, is about 15° higher than that of the maltosazon — 190°- 
191° C. To determine this point it is necessary to filter off the 
osazon, and, after washing with water, to dissolve it upon a filter 
by means of a little hot alcohol. From this alcoholic solution it is 
reprecipitated by water, when it may be collected and dried over 
sulphuric acid. The melting-point is then determined according 
to the usual methods. 

The pentosazons can be readily distinguished from glucosazon by 
their melting-points. 

The amount of lactose which may be found in the urine is far 
too small to give rise to the formation of an osazon when the test 
is directly applied to the urine. 

Polarimetric test. Glucose turns the plane of polarized light to 
the right, but the same may be said of maltose, the degree of polar- 
ization of which is even more intense, so that it may be impossible 
to state in a given case whether such rotation is referable to a large 
quantity of glucose or to a smaller quantity of maltose. The latter 
substance, however, occurs in the urine but rarely, and may be 
recognized not only by the microscopic appearance of its osazon, 
but also by the fact that its power of reduction is increased in the 
presence of sulphuric acid and by the application of heat. 

An error which may further arise with the employment of the 
polarimetric method is referable to the fact that if glucose be 



420 



CLINICAL DIAGNOSIS. 



present in only small amounts, while the urine contains large 
quantities cf /3-oxybutyric acid, the latter turning the plane of 
polarized light to the left, it may happen that the rotation in this 
direction will neutralize or even overcome any rotation to the right 
due to glucose. In such cases, however, the urine will react in a 
positive manner with the other reagents described, and the fer- 
mented urine will, moreover, turn the plane of polarization still 
more strongly to the left, indicating the presence of a dextro- 
rotatory substance, and in all probability of glucose. 

The delicacy of this method varies considerably with the instru- 
ment employed; the figures given below were obtained with the 
apparatus of Lippich, which yields the best results. 

(For a description of this method see the Quantitative Estima- 
tion of Sugar by Means of the Polarimeter.) 



Table showing the Delicacy of the Tests Described. 



Trommer's test 
Fehling's test . 
Ny lander's test 
Fermentation -test . 
Phenylhydrazin test 
Pol arime trie test 



0.0025 per cent. 
0.0008 

0.025 " 

0.1-0.05 " 
0.05-0.001 " 
0.025-0.05 " 



Table showing the Behavior of the Various Forms of Sugar 
which may Occur in the Urine toward the Tests Described. 





Trommer's, viz., 
Fehling's test. 


Ny lander's 
test. 


Fermenta- 
tion-test. 


Phenylhydrazin 

test. 


Polarimetric 
test. 


Glucose, 


Positive reaction. 


Positive 
reaction. 


Positive 
reaction 


Positive reaction ; 
Melting-point 
205° C 


Rotation toward 
the right. 


Levulose, 


Positive reaction. 


Positive 
reaction. 


Positive 
reaction. 


Same osazon ob- 
tained as with 
glucose, only 
more rapidly. 


Rotation toward 
the left. 


Maltose, 


Positive reaction. 


Positive 
reaction. 


Positive 
reaction. 


A maltosazon is 
formed; melting- 
point 190-191° C. 


Rotation toward 
the right. 


Lactose, 


Positive reaction. 


Positive 
reaction. 


No re- 
action, or 
only a 
very faint 
one. 


No reaction in the 
concentration in 
which it may oc- 
cur in the urine; 
melting-point 
200° C 


Rotation toward 
the right ; in- 
creased by boil- 
ing with a 2-5 p.c. 
solution of sul- 
phuric acid. 


Laiose, 


Positive reaction: 
on boiling only 
1.2-1.8 per cent 
more is obtain- 
ed than by the 
polarimeter. 


Positive 
reaction. 


No re- 
action. 


With phenylhy- 
drazin a yellow- 
ish-brown, non- 
crystallizable oil 
is obtained. 


No reaction or 
rotation toward 
the left. 



THE URINE. 421 

Clinically, it is unimportant to search for minute traces of BUgar, 

such as may be found in every normal urine, and the reader is 
referred to special works on physiologic chemistry for a considera- 
tion of the methods generally employed. 

Quantitative Estimation of Sugar. The methods used in the 
quantitative estimation of sugar are essentially based upon the 
qualitative tests described. 

Fehling's method. Fehling's solution, prepared as described 
above, is of such strength that the copper contained in 10 c.c. is 
completely reduced by 0.05 gramme of glucose. If then urine is 
carefully added to this quantity until complete reduction takes 
place, the amount of sugar contained in a given specimen of urine 
can be readily calculated according to the following equation: 

v : 0.05 : : 100 : x, and x = 5 , 

y 
in which y indicates the number of c.c. of urine required to reduce 
the 10 c.c. of Fehling's solution, and x the amount of sugar con- 
tained in 100 c.c. of urine. 

As the best results are only obtained if from 5 to 10 c.c. of urine 
are used in one titration, it is usually necessary to dilute the urine 
to the required degree, in the determination of which the specific 
gravity may serve as a guide. As a general rule, urines of a specific 
gravity of 1.030 should be diluted five times, and if the density be 
still higher, ten times. To be certain that the proper degree of 
dilution has been reached, 5 c.c. of Fehling's solution are treated 
with 1 c.c. of the diluted urine, a little caustic soda and distilled 
water being added to make in all aoout 25 c.c. This mixture is 
thoroughly boiled, and if the fluid still remains blue another 1 c.c. 
of diluted urine added, and so on until the last two tests differ 
by 1 c.c. of urine, the last c.c. added causing a separation of cuprous 
oxide. In this manner the percentage of sugar may be approxi- 
mately determined. Albumin, if present, must first be removed by 
boiling. 

Ten c.c. of Fehling's solution, diluted with 40 c.c. of water, are 
placed in a porcelain dish and boiled. While boiling, the diluted 
urine is added from a burette, 0.5 c.c. at a time, when, as a rule, the 
precipitated cuprous oxide will rapidly settle, so that gradually a 
white bottom maybe seen through the blue fluid, the color of which 
becomes less and less intense upon the further addition of urine 
until, finally, the solution is almost colorless. When this point is 



422 



CLINICAL DIAGNOSIS. 



reached the urine is added only drop by drop, until the decoloriza- 
tion is complete. The degree of dilution multiplied by 5 and the 
result divided by the number of c.c. of diluted urine employed 
will then indicate the percentage-amount of sugar. In the following 
table the percentage results corresponding to the number of c.c. of 
undiluted urine employed will be found: 



Sugar. — Quantity of glucose pro liter corresponding to the number of cubic 
centimeters used for the complete reduction of 10 centimeters of Fehli7ig , s 
solution. 





1 


Vio 


2 /io 


3 /io 


4 /io 


5 /io 


6 /io 


T /io 


8 /io 
27.76 


9 /io 


1 


50.00 


45.44 


41.68 


38.46 


3570 


33.32 


31.24 


29.40 


26.30 


2 


25.00 


23.80 


22.72 


21.72 


20.84 


20.00 


19.22 


18.50 


17.84 


17.24 


3 


16.66 


16 00 


15.62 


15.14 


14.15 


14.28 


13.88 


13.50 


13.14 


1282 


4 


12.50 


12.18 


11.90 


11.62 


11.36 


11.10 


10.86 


10.62 


10 40 


10.20 


5 


10.00 


9.80 


9.60 


9.42 


9.24 


9.08 


8.92 


8.76 


8.62 


8.50 


6 


8.32 


8.18 


8.06 


7.92 


7.80 


7.68 


7.56 


7.44 


7.34 


7.24 


7 


7.14 


7.04 


6.94 


6.86 


6.78 


6.66 


6.56 


6.48 


6.40 


6.32 


8 


6.24 


6.16 


6.08 


6.02 


5.94 


5.88 


5.80 


5.74 


5.68 


5 60 


9 


5.54 


5.48 


5.42 


5.36 


5.30 


5.24 


5.20 


5.16 


512 


5.06 


10 


5.00 


4.94 


4.90 


4.82 


4 78 


4.76 


4.70 


4.66 


4.62 


4.58 


11 


4.54 


4.50 


4.46 


4.42 


4.38 


4.34 


4.30 


4.26 


4.22 


4.20 


12 


4.16 


4.14 


4.12 


4 08 


4.04 


400 


3.98 


3.96 


3.92 


3.86 


13 


3.84 


3.80 


3.78 


3.76 


3.74 


3.70 


3.68 


3.66 


3.62 


3.58 


14 


3.56 


354 


3.52 


3.48 


3.46 


3.44 


3.42 


3.40 


3 36 


3.34 


15 


3.32 


3.32 


3 28 


3.26 


3.24 


322 


3.20 


3.18 


3.16 


3.14 


16 


3 12 


3.10 


3 08 


3.04 


3.04 


3.02 


3.00 


2.98 


2.96 


2.94 


17 


2.94 


2.92 


2.90 


2.88 


2.86 


2.84 


2 82 


2.82 


2.80 


2.78 


18 


2 76 


2.76 


2.74 


2.72 


2-70 


2.70 


2 6S 


2.64 


2.64 


2.64 


19 


2.62 


2.62 


2.60 


2.60 


2.58 


2.56 


2.56 


2.54 


2.52 


2.52 


20 


2.50 


2.50 


2.48 


2.48 


2.44 


2 42 


2.42 


2.40 


2.40 


2.38 


21 


2.38 


2.36 


2.84 


2.34 


2.32 


2.32 


2.30 


2.30 


2.28 


2 28 


22 


2.26 


2.26 


2.24 


2.24 


2.22 


2.22 


2.20 


2.20 


2.18 


2.18 


23 


2.16 


2.16 


2.14 


2.14 


2.12 


2.12 


2.12 


2.10 


2.10 


2.10 


24 


2.08 


2.08 


2.06 


2.06 


2.06 


2.04 


2.04 


2.02 


2.02 


2.02 


25 


2.00 


198 


1.98 


1.96 


1.96 


1.96 


1.94 


1.94 


1.92 


192 


26 


1.92 


1.92 


1.90 


1.90 


1.88 


1.88 


1.88 


1.86 


1.86 


1.86 


27 


1.84 


1.82 


1.82 


1.82 


1.82 


1.80 


1.80 


1.80 


1.80 


1.80 


28 


1.78 


176 


1.74 


1.74 


1.74 


1.74 


1.74 


1.74 


1.74 


172 


29 


1.72 


1.70 


1.70 


1.70 


1.70 


1.68 


1.68 


1.68 


1.68 


1.66 


30 


1.66 


1.66 


1.65 


1.64 


1.63 


1.62 


1.62 


1.62 


1 62 


1.62 



Unfortunately, it is difficult as a general rule to determine exactly 
the point when all the copper has been reduced; i. e., the point at 
which the blue color has entirely disappeared. When it is thought 
that this has been reached, about 1 c.c. should be filtered through 
thick Swedish filter-paper, and the nitrate, which must be absolutely 
clear, acidified with acetic acid and treated with a drop or two of a 
solution of potassium ferrocyanide. If unreduced copper be still 
present in the solution, a brown color will result, indicating that 
sufficient urine has not been added. Bat if, on the other hand, no 
brown discoloration be noted, it is possible that the desired point 
has already been passed, when the titration should be repeated. At 
times the precipitate will not settle at all, and even pass through 



THE URINE. 423 

the filter, so that it is almost impossible to determine the end of 
the reaction. In such cases the following procedure, suggested by 
Cause, will be found serviceable: 

Ten c.c. of Fehling's solution are diluted with 20 c.c. of distilled 
water and treated with 4 c.c. of a -^ per cent, solution of potassium 
ferrocyanide. While boiling, the diluted urine is now added drop 
by drop, until the blue color has entirely disappeared, a precipitate 
not appearing at all with this method. 

In order to obtain reliable results, however, the Fehling's solution 
must be prepared with great care and its strength determined. This 
may be done in the following manner: 0.2375 gramme of crystal- 
lized cane-sugar, pure and dried at 100° C, is dissolved in 40 c.c. 
of distilled w T ater to which 22 drops of a y 1 ^ per cent, solution of 
sulphuric acid have been added. This solution is kept upon a 
boiling water-bath for an hour, when it is allowed to cool and 
diluted to 100 c.c. with distilled water. Twenty c.c. of this solu- 
tion will then contain exactly 0.05 gramme of glucose, corresponding 
to 10 c.c. of Fehling's solution, if this be of the required strength. 
If too strong, so that 21 c.c, for example, of the sugar solution are 
required to obtain a complete reduction of the copper, the strength 
of Fehliug\s solution may be determined according to the equation: 
20 : 0.05 : : 21 : x, and x = 0.0525. If too weak, on the other 
hand, so that 19 c.c, for example, are required, its strength is 
similarly determined: 20 : 0.05 : : 19 : x, and x = 0.0475. If 
necessary, the solution may of course be brought to the exact 
strength in the manner indicated elsewhere, by first making it too 
strong and then ascertaining the required degree of dilution. 

The following method, suggested by Knapp, is said to be better 
than that of Fehling, as daylight is not necessary, as it is applicable 
even in cases in which the amount of sugar is small, as the solution 
keeps for a long while, and as it is simpler. 

The principle of the method depends upon the observation that 
the cyanide of mercury in alkaline solutions is reduced to metallic 
mercury in the presence of sugar. The solution which is required 
should contain 10 grammes of chemically pure, dry cyanide of mer- 
cury and 100 c.c of a solution of sodium hydrate (sp. gr. 1.145) to 
the liter. Twenty c.c. of this solution correspond to 0.050 gramme 
of glucose. 

Knapp' 's method. Twenty c.c of the solution are placed in a 
small retort and diluted with 80 c.c. of water. If we have reason 



424 CLINICAL DIAGNOSIS. 

to suppose that the urine contains less than 0.5 per cent, of sugar, 
40 to 60 c.c. are sufficient. The solution is then heated to the 
boiling-point, when the diluted urine (see below) is added, at first 
2 c.c. at a time, then 1 c.c, 0.5 c.c, 0.2 cc, and 0.1 c.c, as the 
final point is approached. After every addition the solution is 
boiled for one-half minute. As the end- reaction is approached the 
solution begins to become clear, and the mercury, together with the 
phosphates, settles to the bottom. The final point is determined by 
placing a drop of the supernatant fluid upon a piece of clean, white 
Swedish filter-paper, and holding this first over a bottle containing 
concentrated hydrochloric acid and then over one containing a satu- 
rated solution of sulphuretted hydrogen. If all the cyanide of 
mercury has not been reduced, a yellow spot will result, the color of 
which becomes the more manifest if it be compared with one which 
has not been exposed to the action of the sulphuretted hydrogen. As 
soon as the mercury has been entirely reduced the reading is taken. 
Example: Supposing that 15 cc. of urine have been required, the 
corresponding amount of sugar is then found according to the fol- 
lowing equation, 20 c.c of Knapp's solution requiring 0.05 gramme 
of sugar for its reduction : 

15 : 0.05 : : 100 : x : 15 x = 5. and x = 0.333 per cent. 

Precautions: 1. Albumin must first be removed. 

2. The urine should not contain more than 0.5 to 1 per cent, of 
sugar. The urine is hence diluted, if necessary, as with Fehling's 
method. 

Differential density method. This method is very useful in clin- 
ical work, and should be preferred to the more uncertain titration 
with Fehling's solution, unless considerable experience has been 
acquired with this method. 

The specific gravity of the urine is accurately ascertained by 
means of a pyknometer, or a hydrometer accurately graduated to 
four decimals and provided with a thermometer indicating tenths 
of a degree. The temperature at which the specific gravity is taken 
should be that for which the hydrometer has been constructed, the 
urine being heated and cooled to the desired degree. 100 to 200 
cc are then set aside in a flask, after the addition of some yeast 
which has been washed free from mineral material, loosely stop- 
pered or provided with an arrangement like the one shown in the 
accompanying figure (Fig. 97). After twenty-four hours, if but 



THE ujuxi:. 



425 



Fig. 97. 




little sugar be present, or forty-eight hours, if there be much, the 
specific gravity is again determined under the precautions given 
after having filtered the urine. The difference in the specific 
gravity is then multiplied by 230, an empirical factor which has 
been found by dividing the amount of sugar 
ascertained by titration or polarization with 
the difference in the density of the urine 
after fermentation, the result indicating the 
percentage of sugar. The process may be 
hastened if to every 100 c.c. of urine, 2 
grammes of tartrate of potassium and so- 
dium and 2 grammes of diacid-sodium 
phosphate be added with 10 grammes of 
compressed yeast, and the mixture allowed 
to stand at a temperature of from 30° to 
34° C. If but little sugar be present, two 
to three hours will be sufficient. 

That portion of the urine in which the 
specific gravity is determined before fer- 
mentation should really be treated in the 
same manner. It will suffice, however, to 
add 0.022 to the specific gravity found, to make up for the increase 
that should otherwise be observed in the second specimen owing to 
the addition of the salts. 

In every case the urine must be perfectly fresh, as fermentation 
will generally begin spontaneously even after standing a short time. 

Einhorn's method. This will answer very well for ordinary pur- 
poses. Two especially constructed and graduated saccharimetric 
tubes (Fig. 96) are used, one of which is filled with a mixture of 
the suspected urine and yeast, and the other with normal urine and 
yeast, as a control. The tubes are then set aside at a temperature 
of from 30° to 34° C. , when the percentage-amount of sugar in the 
urine is read off from the column of the carbon dioxide present. 
Should the second tube also show a small amount of gas, the figure 
corresponding to this amount is deducted from the first. 

Polar '{metric method. For this purpose the saccharimeter of Soleil- 
Ventzke is very convenient (Fig. 98). This consists essentially of a 
NicoPs prism, a, which may be rotated about the axis of the appa- 
ratus; a second NicoFs prism at d ; vertically placed compensating 



Flask for the approximate esti- 
mation of sugar by fermentation. 
(v. Jaksch.) 



prisms, consisting of dextro-rotatory quartz at e, which may be 



m 



CLLSJCAL DIAGS 



moved horizontally by means of a raek-and-pinion adjustment, this 
being tnrned by a milled head at 7;, so that light can pass through 
a thicker or thinner layer of the dextro-rotatory quartz. At f there 
is a plate of gyro-rotatory quartz cut perpendicularly to the optical 
axis, covering the entire field of vision; at h biqnartz plates of 
Soleil, and at i an Icelaod-spar crystal; b c represents a small tele- 
scope, by means of which the biqnartz plates can be accurately 



Fig. 98. 




Soleil-Venixke'E saccharrmeter. 



focussed. "Wlien the compensation-prisms of this apparatus are in 
a certain position, the gyro-rotation of the plate /will be exactly 
compensated and the two halves of the field of vision present the 
same color, while the zero of the scale x will coincide with the zero 
of the vernier y, arranged on the apper surface of the compensators. 
Any change in this position produced by turning the screw 7; will 
cause the appearance of a different color in each half of the field of 
vision. If now, with a zero-position, an optically active dextro- or 
gyro-rotatory substance be interposed, the color of each half of the 
field of vision will become altered, but may be equalized again by 
changing the position of the compensators, the degree of change 
necessary to produce this result constituting an index of the power 
of rotation of the solution interposed in the tube m. 

Soleil-Ventzke' s apparatus is constructed in such a manner that 
if a solution of glucose be employed, the length of the tube m being 






THE URINE. 427 

10 cm., every entire line of division on the scale will indicate 1 per 

cent, of sugar. 

The tube of the saccharimeter should be carefully washed out 
with distilled water, and at least once or twice with the filtered 
urine, when it is placed on end upon a flat surface, and filled with 
the urine to such a degree that this forms a convex cup at the end. 
The little glass plate is now carefully adjusted, so as to guard 
against the admission of bubbles of air. The metallic cap is then 
placed in position, care being taken to avoid undue pressure. The 
examinations are made in a dark room, an ordinary lamp being 
used, and several readings taken, until the differences do not amount 
to more than one-tenth or two-tenths per cent. The tubes should 
be thoroughly cleansed immediately after the experiment. 

In every case the filtered urine should be free from albumin, 
and, if markedly colored, previously treated with neutral acetate of 
lead in substance and filtered. 

If it be desired to demonstrate only the presence of sugar, the 
compensators are first brought to the zero-position. If now, upon 
the interposition of the tube filled with urine, a difference in the 
color of the two halves of the field of vision be noted, the presence 
of an optically active substance in the urine may be assumed, and 
if at the same time the deviation be to the right, the presence of 
glucose is rendered highly probable, while a deviation to the left 
will generally be referable to levulose or ,2-oxybutyric acid. Indican, 
peptones, cholesterin, and certain alkaloids, it is true, also turn the 
plane of polarization to the left, but as a rule these substances need 
not be considered, cholesterin occurring but rarely, while indican 
in diabetic urines is usually present in only small amounts, and a 
concurrence of sugar and peptones has not as yet been observed. 
Lactose and maltose, which also turn the plane of polarization to 
the right, may be distinguished from each other and from glucose 
by the phenylhydrazin test. Levulose turns the plane of polariza- 
tion to the left. Oxybutyric acid is practically always associated 
with the presence of glucose, and may be recognized by allowing 
the urine to undergo fermentation, when the filtered urine will 
become distinctly gyro-rotatory. 

Comparatively little interest, from a clinical point of view, attaches 
to the occurrence of other forms of sugar in the urine. 

Lactose. Lactose may be found in the urine near the end of 
gestation, but more especially in nursing-women in whom the flow 



428 CLISICAL DIAGXOSIS. 

of milk is impeded, owing to the existence of mastitis, for example. 
It lias also been stated that lactosuria occurs in nursing-women who 
have well-developed breasts, in the absence of any obstruction, and 
that the good qualities of a wet-nurse are indicated by a copious and 
persistent elimination of milk-sugar. Its presence may be inferred 
if a positive result is obtained with Trommer's and Nylander's tests, 
while the phenylhydrazin and fermentation tests give negative re- 
sults, although an osazon can be obtained from the pure substance, 
and although this undergoes a certain form of alcoholic fermentation. 

Lemaire, who has recently investigated this subject, found that 
the urine of nineteen women examined in this direction apparently 
contained no sugar during the last twelve days preceding confine- 
ment (Trommer's and Xylander's test), while a positive reaction 
was obtained with Trommer's reagent in two cases, and with 
Ny lander's reagent in thirteen cases after confinement. The 
phenylhydrazin test was negative in all nineteen before and posi- 
tive after confinement, when this was direct/}/ applied to the substance, 
isolated according to Baumann's method. The percentage varied 
between 0.013 and 0.438 per cent., and appeared to be uninfluenced 
by the act of nursing. 

Levulose. Levulose is occasionally found in diabetic urines 
together with glucose, its presence being often indicated by the fact 
that a polarimetric examination shows a deviation to the left or 
none at all, while the other tests for sugar indicate the presence of 
a reducing substance. 

Maltose. Maltose together with glucose was found in the urine 
of a patient supposedly the subject of pancreatic disease, associated 
with an acholic condition of the stools. Its recognition is practically 
dependent upon the formation of its osazon and a determination of 
the melting-point of the latter. 

Dextrin. In one case of diabetes dextrin appeared to take the 
place of glucose. It may be recognized by the fact that upon the 
application of Fehling's test the blue liquid first becomes green, 
then yellow and sometimes dark brown. 

Laiose. Laiose occurs at times in the urine of diabetic patients. 
It is essentially characterized by the fact that by titration with 
Fehling's solution from 1.2 to 1.8 per cent, more sugar is indicated 
than by the polarimetric method. 

Pentoses. To judge from recent observations, traces of pentoses, 
viz., xylose, arabinose, and rhamnose, may be found in every urine. 



THE URINE. 429 

Large quantities were first observed by Salkowski and Jastrowitz 

in the urine of a morphine habitue, where the pentosuria alternated 
with glycosuria. A similar ease was reported by Reale, and Kiilz 
and Vogel found Large quantities in diabetes. Such urines reduce 
Fehling's solution, and give rise to the formation of an osazon 
when treated with phenvlhydrazin. The osazon, however, can be 
readily distinguished from that obtained from glucose, maltose, or 
lactose, etc , by the melting-point. The fermentation-test is nega- 
tive. Arabinose and rhamnose turn the plane of polarized light 
to the right, while xylose remains indifferent. When present in 
notable amounts they are readily detected with Tollens* reagent : 
To this end phloroglucin is dissolved in 5 to 6 c.c. of concentrated 
hydrochloric acid by the aid of heat, so that a slight excess is 
present. This solution is divided into two equal parts and allowed 
to cool. To one portion 0.5 c.c. of the urine to be examined is added, 
and to the other an equal amount of normal urine of the same specific 
gravity. Both specimens are placed in a beaker containing boiling 
water, when in the presence of pentoses a deep red color will first 
be obseiwed at the top, which gradually extends throughout the 
mixture, while the normal specimen scarcely changes in color. In 
the presence of 0.1 per cent, a positive reaction is still obtained, 
which is especially marked if the urine has been previously decol- 
orized with animal charcoal. After dilution with an equal volume 
of water the coloring-matter may be extracted with amyl alcohol. 

Animal gum. Animal gum, according to modern researches, is 
a constant constituent of normal urine, but of no clinical interest. 

Inosit. Inosit does not occur normally in the urine, but may be 
demonstrated after the ingestion of large amounts of water. Patho- 
logically it has been found in cases of diabetes insipidus and in 
albuminuria, but is of no especial interest. 

Urinary Pigments and Chromogens. 

In considering the subject of urinary pigments it is necessary to 
differentiate sharply between such pigments as occur preformed in 
the urine and others that only appear upon the addition of certain 
reagents which have the power of decomposing their chromogens. 
Until quite recently this subject was in a most confused condition, 
and even now our knowledge can only be regarded as rudimentary ; 
for, notwithstanding the fact that numerous investigations have been 
made with a view to determine the source of the color of normal 



430 CLINICAL DIAGNOSIS. 

urine, this problem is not even vet definitely solved, and it is only 
possible to say at the present time that urochrome and possibly a 
certain indoxyl derivative are to some extent responsible for the 
normal color of the urine. 

Under normal conditions urochrome and uroerythrin, to which 
latter the red color of urate sediments is due. are the only known 
pigments occurring preformed in the urine, while indigo-red and 
indigo-blue, derived from indoxyl sulphate and indoxyl glycu- 
ronate, may be artificially produced. Pathologically, on the other 
hand, various other pigments may be found, occurring in the urine 
either free or in the form of chromogens. Among the former 
may be mentioned haemoglobin, methasmoglobin, haematic. Intern ato- 
porphyrin, urorubroheematin. nrofnscohaematin, urobilin, the biliary 
pigments and melanin, while abnormal chromogens are seen follow- 
ing the ingestion of certain drags, such as santonin, senna, rheum, 
iodine, etc.. as also in cases of poisoning with carbolic acid, creosote, 
etc. The occurrence of some of these substances, such as the various 
forms of blood-pigment, the biliary pigments, and indigo, viz., 
indican. is of considerable clinical interest, while others again are 
only of minor importance. 

Normal Pigments. Urochrome. To the presence of this pig- 
ment, which appears to be identical with the normal urobilin of 
MacMunn, but which should not be confounded with the pathologic 
urobilin of J'-'.uL the normal yellow color of the urine appears to be 
due to a certain extent. It is undoubtedly derived from bilirubin, 
which in turn is referable to the htematin and haemoglobin of the 
blood and results from the bilirubin secreted into the intestinal tract 
by a process of oxidation, and not of reduction, as is generally stated. 
Such a transformation, according to our present knowledge, may, 
however, also occur directly, without the intervention of bilirubin, 
as urochrome is found in the urine of dogs in which the bile is pre- 
vented from entering the intestinal tract by the establishment of a 
biliary fistula. An increased amount is similarly found in cases in, 
which resorption of large extravasations of blood is taking place in 
the body — in short, whenever an increased destruction of red cor- 
puscles is noted; while under the opposite circumstances — i. e., in 
conditions associated with a definite formation of red corpuscles, as 
in certain forms of anaemia, chronic parenchymatous nephritis, 
diabetes, diseases of the bone-marrow, etc. — it occurs in diminished 
amount. 



THE URINE. 431 

In order to obtain nrochrome from normal urine this is acidu- 
lated with l-'l grammes pro liter of dilute sulphuric acid, filtered, 
aud saturated with ammonium sulphate in substance, when the 
flakes which are found in an excess of the salt are dried and treated 
with warm, slightly ammoniacal absolute alcohol, the pigment being 
obtained upon evaporation of the alcohol. An alcoholic solution of 
urochrome, like the urobilin of Jaffe, exhibits a beautiful greenish 
fluorescence when treated with ammonia and a few drops of a solu- 
tion of zinc chloride, but, unlike the latter substance, its acidulated 
alcoholic solutions present a broad band of absorption at " F," 
extending more to the left than to the right of this line, while the 
remainder of the spectrum at the same time is absorbed to the right 
end from a point somewhat to the left of " G." 

Uroerythrin. Uroerythrin is the pigment which imparts the red 
color to crystals of uric acid and urate sediments. In pathologic 
conditions it is seen especially in cases of hepatic insufficiency, in 
which the liver, owing to a greatly increased destruction of red 
corpuscles, is unable to transform all the blood-pigment which 
is carried to it into bile-pigment, and also where an absolute 
insufficiency on the part of the hepatic cells exists, so that the 
organ is not even capable of causing the transformation of a normal 
amount of haemoglobin. Uroerythrin is thus seen in notable quan- 
tities in cases of pneumonia, malarial fever, erysipelas, spinal curva- 
ture, hepatic cirrhosis, carcinoma of the liver, etc. Chemically, its 
close relation to haemoglobin, haernatoidin, and bilirubin is seen 
from the following analyses of the various pigments: 

C H N O S Fe 

Haemoglobin, 53.85 7.32 16.17 0.39 0.43 

Haematoidin, 65.05 6.37 9.51 

Bilirubin, 67.83 6.29 9.79 16.79 

Uroerythrin, 62.51 5.79 31.70 

When present in large amounts uroerythrin is readily recognized 
by the salmon-red color which it imparts to urinary sediments. 
Otherwise it is best to precipitate the urine with neutral acetate of 
lead, barium chloride, or a similar reagent, when in the absence of 
uroerythrin a milky-white precipitate is obtained, a pale rose-colored 
sediment indicating the presence of the pigment in appreciable 
amounts, a more pronounced rose-color being produced by large 
quantities. In every case at least ten to fifteen minutes should be 



C s H 7 y - = 


CJBJSO 




Indol. 


Indoxyl. 




c,H-yo - so 


OH 

2X 0H _ 


so, x - h-«:> 

" x OH 


Indoxyl. 




Indoxyl-sulphate. 


S °<0H 


- Na HPO = - : -yaBVPO, 
" X OXa 


Indoxyl-sulphate. 




Indoxyl-sodium sulphate. 



432 CLISICAL DIAGNOSIS. 

allowed to elapse before forming a definite conclusion, so that the 
sediment may have abundant time to settle. 

Normal Chromog-ens. The chromogens occurring in normal 
urine are indiean, uroha?matin, and an unknown chromogen which 
yields urorosein when treated with mineral acids. 

Indiean. It has already been- pointed out (see Sulphates) that 
the indol formed during the process of intestinal putrefaction is 
oxidized to indoxyl in the blood; this, entering into combination 
with sulphuric acid, is eliminated in the urine as sodium or potas- 
sium indoxyl-sulphate, or indiean, as represented by the equations: 



:: 



HI. 



Formerly it was thought that indiean was also formed within the 
tissues of the body in the absence of putrefactive organisms (this view 
having been held especially by Salkowski ). Further researches, how- 
ever, have demonstrated beyond a doubt that micro-organisms are 
always concerned in the production of indiean, and that in health the 
large intestine is its only source. Thus, Baumann, who succeeded 
in absolutely disinfecting the intestinal tract in a dog by means of 
large doses of calomel, observed that all traces of indiean, as also of 
phenol and paraeresol, disappeared from the urine. According to 
Senator, moreover, indiean does not occur in the urine of newly 
born infants which have not as yet received nourishment. This 
observation is a strong point in favor of Nencki'a teachings that 
indol is a specific product of albuminous putrefaction in the presence 
of organized ferments, as putrefiable substances are present, but no 
putrefactive organisms. Tuczek's observations on abstinence from 
food in eases of insanity, in which indiean was only observed in the 
urine when albumins, though in minimal amounts, were ingested, 
also speak very strongly against Salkowski'a theory. Finally, it has 
been demonstrated that in cases in which an artificial anus is estab" 
lished near the distal end of the ileum the conjugate sulphates disap- 
pear almost entirely from the urine, while they reappear in normal 



THE URINE. 433 

amount as soon as the connection between the small and large intes- 
tines has been re-established. 

The amount of indicao normally eliminated in the urine varies 
somewhat with the character of the diet, Jaffe having found (>.6 
milligrammes in 1000 c.c. of urine as au average of eight observa- 
tions. The largest quantities excreted in health are found after 
a liberal indulgence in animal food, particularly the so-called red 
meats, while the smallest amounts are observed during a milk or 
kefir diet. By means of the latter article, indeed, the greatest dimi- 
nution in the degree of intestinal putrefaction may be effected in 
man. In pathologic conditions an increased elimination of indican 
is observed : 

1. In all cases associated with an increased degree of intestinal 
putrefaction. As there appears to be little doubt that this is largely 
regulated by the acidity of the gastric juice, an iucreased indicanuria, 
according to personal observations, is encountered when anachlor- 
hydria or hypochlorhydria exists. It has been pointed out else- 
where that it is possible to form a fairly accurate idea of the amount 
of free hydrochloric acid in the gastric juice by an examination of 
the urine in this direction. Large quantities of indican are thus 
eliminated in cases of carcinoma of the stomach, and exceeded only 
by those observed in cases of ileus, so that this symptom, in the 
author's estimation, is one of considerable value in differential diag- 
nosis, and one, moreover, which has not as yet received the attention 
which it undoubtedly deserves. Exceptions to this rule are at times, 
though rarely, met with, for which it is, however, impossible to 
account definitely at the present time. Large quantities of indican 
are also observed in cases of acute, subacute, and chronic gas- 
tritis, of whatever origin. In the course of personal observations 
in this direction the author was struck with the curious phenomenon 
that in cases of ulcer of the stomach, notwithstanding the simulta- 
neous occurrence of hyperchlorhydria, an increased elimination of 
indican, contrary to what is usually seen in hyperchlorhydria, refer- 
able to other causes, is quite constantly found. Possibly the exist- 
ence of muscular atony noted in those cases may serve to explain 
this apparent incongruity, but it is as yet impossible to offer a satis- 
factory explanation of the phenomenon. Rememberiug the origin 
of indican, and the relation which the amount eliminated bears to 
the degree of intestiual putrefaction, it will be unnecessary to enume- 
rate the long list of diseases in which an increased indicanuria has 

28 



-.:-. 



:i:.y:;^i zz±~y; ;:.- 




r^'-^r: 




i ::.- 



ill- -r.-- :i: r'..-_ .1:: "i :•- _-i :i : . .- .:::-: ?::■: - .: :_ 2:17 :^ 
aavu^ Halt Ike stndy of 

l---:r ;: - :~ , -..r. : :" = 

-.; .;, ■-.:■- ■ '. . ■ i: :'■:■'■■> : „; : V •.:«, 

fkms he gmm&i, 

- ::--v-l —:i ijir-x-i." :r.: }..:_• i .: Li 

i 2 1 : : 1 : : 17 '. - 1 : ": '. : iz 1 :::: •' - : : .1 :-. '■- 

7:^,1: l: "- sL=if z^= ni ,:- .- :i- :lif :•::-: r-i_.--: :: :_- 



" " LIT ~— 1_ - 1 " " . — 1 1- - - " . Z -.. 



warn as umpananm, as 



"i.:-T .- Li :.rr?Li_.. ir 

"r-.l — 1L11 — -r-7-r " -t 






THE URINE. 435 

phenomenon must be regarded as a medical curiosity. The blue pig- 
ment which may be obtained from urines has been variously described 
as Prussian-blue, urocyauin, cyanourin, Harnblau, uroglauoin, chol" 
eraic urocyauin, but has been ultimately shown to be indigo-blue' 
derived from a colorless mother-substance present in every urine to 
a greater or less extent, which has been named indican, and which 
has been shown to be identical with the uroxanthin of Heller and 
Thudichum's choleraic urocyaninogen. 

Test for indican. Unfortunately the methods which so far have 
been proposed for the purpose of quantitatively determining the 
amount of indican in the urine are not only inaccurate, excepting, 
perhaps, the spectroscopic method devised by Muller, but, what is 
more, are too lengthy and complicated to be of value to the prac- 
tising physician. As a consequence the observations made by almost 
all observers are based upon an approximative estimation only. For 
practical purposes such a method, particularly the one to be pres- 
ently described, is sufficient, the degree of increase which interests us 
of course, more particularly being judged fairly accurately thereby, 
as is quite generally admitted by those who have employed this 
method, and have compared the same with the results obtained 
with the more complicated ones mentioned. 

The most convenient method is a modification of that of Jaffe., 
suggested by Stokvis : 

The urine of twenty-four hours is carefully collected and a speci- 
men taken for examination. A few c.c. of urine are mixed with an 
equal amount of concentrated hydrochloric acid, and 2 or 3 drops of 
a strong solution of sodium hypochlorite, calcium hypochlorite, or 
common saltpeter, and 1-2 c.c. of chloroform added. The mixture 
is thoroughly agitated and set aside. The indigo which has been 
set free in this manner is taken up by the chloroform, coloring this 
blue to a greater or less extent, the degree of increase as compared 
with the normal being determined by the intensity of the color. 
Albumin need not be removed. Bile-pigment, which interferes 
with the reaction, is removed by means of a solution of subacetate 
of lead carefully added in order to avoid an excess. Urines pre- 
senting a very dark color may be cleared in the same manner. 
Potassium iodide, which, if present, will, owing to the liberation of 
free iodine, color the ehloroform more or less of a carmine, must also 
be removed. For the sake of comparison, it is well to employ the 



436 CLINICAL DIAGNOSIS. 

same quantities of urine and reagents in every case, marked tubes 
being very convenient for this purpose. 

In this connection it may be said that the author has found this 
method to be at the same time a fairly sensitive test for albumin, 
the mixture of hydrochloric acid and urine upon the addition of the 
oxidizing agent presenting a well-marked cloudiness on the surface 
of the liquid, which gradually extends downward. 

Urohcematin. Uroh^ematin appears to be the chromogen of the red 
pigment of the urine, and is very likely closely related to indoxyl. 
Little, however, is known of its chemical composition or of its 
mode of formation. In all probability the red pigment which 
may be obtained from this substance is identical with other red 
pigments which have been described from time to time as occur- 
ring in the urine, such as that of Scherer, the urrhodin of Heller, 
the urorubin of Plosz, Schunk's indirubin, Bayer's indigo-purpurin, 
Giacosa's pigment, and also the indigo-red obtained by Rosenbach 
and Rosin by careful oxidation of the urine with nitric acid. 

Further investigations are necessary before this subject is fully 
understood, but bearing in mind the probable origin of urohsematin 
from indoxyl, it would possibly be best to speak of the red pigment 
as indigo-red. 

The presence of urohsematin in normal urine — i. e., a chromogen 
yielding a red pigment when treated with certain reagents — may be 
demonstrated by shaking urine with chloroform and decanting after 
several days, when the addition of a drop of hydrochloric acid to 
the chloroform extract will cause the appearance of a beautiful rose- 
color, varying in intensity according to the amount of the chromogen 
present. 

In accordance with the view that urohcematin is an indoxyl deriva- 
tive, its clinical significance is similar to that of indican (which see). 
The purplish color so often obtained in the chloroform extract, when 
Stokvis' modification of Jaffe's indican test is employed, is due to 
a mixture of indigo-blue and indigo-red. Indican, however, always 
appears to be present in larger amounts than urohaBmatin ; and in 
normal and usually also in pathologic urines a red color is not 
obtained with the test mentioned. In a few isolated cases of ileus, 
peritonitis, and carcinoma of the stomach the author found more 
indigo-red than indigo-blue. 

The so-called " Reaction of Rosenbach " is a convenient test for 
indigo-red when this is present in increased amounts: the boiling 



the urim:. 437 

urine is treated drop by drop with concentrated nitric acid, when in 
the presence of large amounts of indigo-red it will assume a dark 
Burgundy color, which sometimes takes on a bluish tinge if held to 
the light. Owing to a precipitation of the pigment the mixture at 
the same time becomes cloudy, the foam assuming a blue color. In 
well-marked cases the Burgundy color does not appear to be changed 
by the further addition of nitric acid, but will sometimes, when 10- 
20 drops of the acid have been added, suddenly turn from red to 
yellow. This reaction Rosenbach regarded as symptomatic of 
various forms of severe intestinal disease associated with an im- 
peded resorption throughout the entire intestinal tract. Ewald like- 
wise noted this reaction in cases of extensive disease of the small 
intestine, in carcinoma of the stomach, acute and chronic peritonitis, 
but obtained negative results in carcinoma of the colon, stricture of 
the oesophagus, chronic diarrhoea, etc. Rosenbach's reaction should 
be dewed in the same light as a highly increased elimination of indi- 
can; the author has met with the same in all conditions associated 
with greatly increased intestinal putrefaction, and, as did Ewald, 
failed to note the reaction iu a few cases of occlusion of the large 
intestine, in which an increased elimination of indican is likewise 
never observed. 

Uroroseinogen. In addition to indican and urohsematin still an- 
other chromogen, which yields a rose-red pigment when treated with 
mineral acids, appears to occur in normal urine, although in small 
amounts. Beyond the fact that the chromogen is no conjugate sul- 
phate, practically nothing is known of its chemical nature. The 
pigment, which has received the name urorosein, or Harnrosa, 
appears to be identical with Heller's urophain. Urorosein may 
be best demonstrated by treating 5-10 c.c. of urine with an equal 
amount of concentrated hydrochloric acid and 1 or 2 drops of a 
concentrated solution of bleaching-powder, when iu the presence of 
much indican the mixture first assumes a dark-greenish, blackish, 
or dark-blue color, owing to the formation of indigo. When the 
mixture is shaken with chloroform the supernatant fluid will exhibit 
a beautiful rose-color, due to the urorosein. This may then be 
extracted with amyl alcohol and separated from any other pigment 
present at the same time by shaking with sodium hydrate, whereby 
the solution is decolorized. Upon the addition of a drop or two of 
hydrochloric acid to the alcoholic extract the rose-color will reappear. 
Such solutions, however, soon become decolorized upon standing. A 



438 CLINICAL DIAGNOSIS. 

rose- red ring, referable to this pigment, is also frequently obtained 
in pathologic urines when the ordinary nitric-acid test is employed. 

While normally urorosein can only be obtained in traces, appre- 
ciable amounts are often met with in pathologic conditions associated 
with grave disturbances of nutrition, as iu nephritis, diabetes, carci- 
noma, and dilatation of the stomach, pernicious anaemia, typhoid 
fever, phthisis, and at times in profound chlorosis, etc. A vege- 
table diet also appears to cause au increase in the amount of the 
ehrornogen. 

Pathologic Pigments and Chroniogens. The blood-pigments. 
The blood-pigments proper which may occur in the urine have 
already been considered (see p. 409), and in this connection it will 
only be necessary to refer briefly to the occasional presence of haeni- 
atin, urorubrohsernatin, urofuscohaematin, and haematoporphyrin. 

Hcematin is only rarely seen. In order to demonstrate its pres- 
ence the urine is rendered strongly alkaline with ammonia, filtered, 
and the filtrate examined spectroscopically, when the spectrum shown 
in Fig. 6 will be noted, which may be changed into the spectrum 
represented in Fig. 7 by the addition of ammonium sulphide. 

Urorubrohcematin and urofuscohvematin are two pigments which 
were observed by Baumstark in the urine of a ease of pemphigus 
leprosus complicated with visceral lepra, and which appear to be 
closely related to haernatin. The color of the urine in this case 
varied between dark red and brownish-red, strongly suggesting the 
presence of blood. In order to separate out the pigments the urine 
was dialyzed and the contents of the dialyzer dissolved in sodium 
hydrate solution. Upon the addition of hydrochloric acid to this 
solution a brown pigment separated out in flakes, while a second 
pigment remained in solution,' imparting to it a beautiful red color. 
Upon filtration the acid filtrate was again subjected to dialysis, 
when the red pigment likewise separated out. The former sub- 
stance Baumstark termed urorubrohaematin, and the latter urofus- 
cohaematin. 

Urohoematopoiyhyrinh&s the formula C 16 H 18 N 2 3 , and is probably 
closely related to the haematoporphyrin resulting from the action of 
sulphuric acid upon haematin. MacMunn found a pigment answer- 
ing the description of this substance in the urine in cases of rheuma- 
tism, Addison's disease, pericarditis, and paroxysmal haemoglobin- 
uria, which he termed urohaematin, but which in all probability was 
haematoporphvrin. Le Xobel found the same pigment in two cases 



THE URINE. 439 

of hepatic cirrhosis and in one case of croupous pneumonia. More 
receutly hamiatoporphyrin has been repeatedly noted in the urine 
during a long-continued administration of sulphonal, trional, and 
tetronal, as also in cases of lead-poisoning and intestinal hemor- 
rhages. Clinically its occurrence does not appear to be of any diag- 
nostic significance, and recent researches have shown that in traces 
at least it is present in every urine. Urines rich iu hsematopor- 
phyrin present an abnormal color, varying from a sherry or port- 
wine tint to Bordeaux. Albumin in uncomplicated cases is not 
present, and Inematoporphyrin itself does not give the albumin 
reactions. In urines presenting the color just described hsemato- 
porphyrin may be tested for in the following manner: 

Thirty c.c. of urine are treated with an alkaline solution of barium 
chloride. The precipitate, after having been washed with water and 
then with absolute alcohol, is extracted with ordinary alcohol acidu- 
lated with hydrochloric acid, by rubbing in a mortar. The solution 
thus obtained will present a reddish color in the presence of haBma- 
toporphyrin, and its nitrate yield the characteristic spectrum of the 
latter substance; i.e., four bands of absorption, of which two are 
broad and dark and two light and narrow. The former alone are 
characteristic, and frequently the only ones visible. One of these 
extends beyond "D" into the red portion of the spectrum, while 
the other is situated between "b" and " F." Of the other two 
bands, one may be seen between " C" and " D," and the other 
between " D " and " E," nearer " E" (Fig. 9). 

In conclusion it may be said that a chromogen of hsernatopor- 
phyrin also usually occurs in urines containing the free pigment, 
which probably explains why such urines gradually become darker 
on standing. 

Biliary pigments. Of the four biliary pigments, viz., bilirubin, 
biliverdin, biliprasin, and bilifuscin, the former alone is met with in 
freshly voided urines, while the others may form upon standing, 
being oxidation-products of bilirubin. As this pigment is never 
found in normal urines, its occurrence may be regarded as an 
infallible symptom of disease. 

In health it will be remembered that bilirubin, C 16 H 18 N 2 3 , formed 
in the liver from blood-pigment, is eliminated into the small intes- 
tine, in which it is transformed into hydro-bilirubin and largely 
excreted as such in the feces, while a small portion is resorbed into 
the blood and eliminated in the urine as urochrome or normal urobilin. 



440 " CLINICAL DIAGNOSIS. 

Whenever then the outflow of bile into the intestines becomes impeded 
bilirubin is absorbed by the lymphatics and eliminated in the urine, 
icterus at the same time resulting. 

Among the numerous causes which give rise to choluria under 
such conditions may be mentioned obstruction of the biliary ducts 
and especially of the common duct, referable to simple swelling of 
its mucous membrane, as in the ordinary forms of catarrhal jaun- 
dice ; it may also be due to the presence of a biliary calculus, to 
parasites, compression of the duct by tumors of the liver, the gall- 
bladder, the duct itself, and of neighboring structures, particularly 
the pancreas, stomach, and omentum. Whenever the blood-press- 
ure in the liver is lowered, so that the tension in the smaller biliary 
ducts becomes greater than that in the veins, choluria likewise results. 
The icterus occurring under these conditions has been termed hepa- 
togenic icterus, in contradistinction to the form observed in cases in 
which the liver has either totally or partially lost the power of 
forming bile, owing to the existence of degenerative processes affect- 
ing its glandular epithelium, as in cases of acute yellow atrophy, or 
in which the destruction of red corpuscles is going on so rapidly 
and so extensively that the organ is incapable of transforming into 
bilirubin all the blood-pigment which is carried to it. This occurs 
in pernicious anaemia, malarial intoxication, typhoid fever, poison- 
ing with arseniuretted hydrogen, etc. The icterus neonatorum is 
probably to a certain extent also dependent upon the latter cause. 
To this form the term hcematogenic icterus has been applied. In 
such cases the occurrence of bilirubin in the urine can only be 
explained by assuming that a transformation of blood coloring- 
matter into bilirubin has taken place in the blood itself or in other 
tissues of the body. As a matter of fact, it appears to be quite 
generally accepted that such a transformation can actually occur 
outside of the liver, as the hsematoidin which may be found in old 
extravasations of blood seems to be identical with bilirubin. On 
the other hand, however, the existence of a hsematogenic icterus is 
positively denied, especially by Stadelmann. In accordance with 
his view it may actually be demonstrated that in cases of pernicious 
anaemia, malaria, etc., the urine does not contain bilirubin, but 
usually urobilin. In cases of this kind which the author had 
occasion to examine bilirubin was never found. Further investi- 
gations are necessary to settle this question definitely. 

Usually the presence of biliary pigment may be recognized by 



THE URINE. 441 

ocular inspection, as urines which contain this in notable amounts 
present a color varying from a bright yellow to a greenish-brown. 
Any morphologic elements which may occur in the sediment are 
stained a golden-yellow, aud the same color is imparted to the foam 
of the urine, as well as to the filter-paper used in its filtration. At 
times, however, and particularly in cases in which the icterus is only 
beginuing to appear, the presence of bilirubin is not infrequently 
overlooked, and urines containing urobilin in large amounts may be 
similarly mistaken for icteric urines. In doubtful cases, therefore, 
whether icterus exists or not, but in which the urine presents an 
intense yellow color, it is necessary to have recourse to chemical 
tests. A large number of these have been devised for the purpose 
of demonstrating the presence of bilirubin, all of which are fairly 
reliable. Only those will be described here which the author has 
had occasion to employ personally and which deserve especial con- 
sideration as being the most delicate. 

Smith's test , as modified by Rosin: 5-10 c.c. of urine are placed 
in a test-tube and treated with 2 or 3 c.c. of tincture of iodine 
which has been diluted with alcohol in the proportion of 1 : 10, 
in such a manner that the iodine solution forms a layer above the 
urine. In the presence of bilirubin a distinct emerald-green ring 
will be seen to form at the zone of contact. This test can be highly 
recommended as being the simplest, and is not surpassed in delicacy 
by any other. 

HupperVs test: 10-20 c.c. of urine are precipitated with milk of 
lime (a solution of barium chloride is, perhaps, still more conve- 
nient), and the precipitate, after filtering, brought into a beaker by 
perforating the filter and washing its contents into the latter with 
a small amount of alcohol acidulated with sulphuric acid. The 
mixture is boiled, when in the presence of bilirubin the solution 
assumes a bright emerald-green color. Hupped/ s test is as delicate 
as that of Smith, but not so convenient for the needs of the prac- 
tising physiciau. 

Gmelin's test, as modified by Rosenbach : The urine is filtered 
through thick Swedish filter-paper, when the latter is removed and 
a drop of concentrated nitric acid, which has been allowed to stand 
exposed to the air for a short time, is placed upon its inner surface. 
In the presence of bilirubin rings presenting the colors of the rain- 
bow will be seen to form around the nitric acid. 

Gmelin's test: The urine is treated with nitric acid, which is carried 



442 CLINICAL DIAGNOSIS. 

to the bottom of the test-tube by means of a pipette, so as to form 
a layer beneath the urine, when a color-play, as already described (p. 
396), will take place at the line of contact between the two fluids, 
the green color being the most characteristic. 

In this connection a few words may also be said of the occurrence 
in the uriue of biliary acids and cholesterin. 

Biliary acids. These may be demonstrated in the urine whenever 
bile-pigment is present, so that their clinical significance is essentially 
the same as that attaching to bilirubin. Their demonstration is, 
however, attended with such difficulties that the methods devised for 
this purpose may well be omitted here (see also p. 196). 

Cholesterin. Cholesterin has never been found in icteric urines 
aud is only rarely seen in other pathologic conditions. It has been 
observed in cases of chyluria, fatty degeneration of the kidneys, 
diabetes, in one case of epilepsy, and in two cases of pregnancy. 
v. Jaksch has noted the presence of cholesterin crystals in a urinary 
sediment in a case of tabes and cystitis. The author found choles- 
terin crystals in the sediment in a case of acute nephritis. The 
urine was of a dark amber-color, cloudy, of an acid reaction, and a 
specific gravity of 1.028. In the sediment numerous hyaline and 
epithelial casts and some red blood-corpuscles were found. Guter- 
bock described a urinary calculus obtained from the bladder of a 
woman which consisted almost entirely of cholesterin (see also Feces). 

Beginners at times regard the spangles of urea nitrate seen in urines 
rich in urea, after the addition of nitric acid, as cholesterin, an error 
which should be guarded against. 

Pathologic urobilin. This pigment should not be confounded with 
the urochrome or normal urobilin described above, to which it is 
closely related, but from which it may be readily distinguished by 
means of the spectroscope. Gautier states that pathologic urobilin 
may be obtained from urochrome by submitting the latter to the 
action of reducing agents. Like normal urobilin it is derived from 
the coloring-matter of the blood and bilirubin, merely representing 
a lower form of oxidation than normal urobilin. It is said to be 
identical with the stercobilin found in the feces. While its occur- 
rence in the urine is essentially a pathologic phenomenon, it is at 
times also met with in normal urines, and appears to be derived 
from a special chromogen, urobilinogen, from which it may be set 
free by the -addition of an acid. From its frequent occurrence in 
febrile urines pathologic urobilin has also received the name febrile 



THE URINE. 443 

urobilin. It is, however, also observed in many other conditions, 
and especially in cases presenting the so-called hematogenic form of 
icterus, from which fact, indeed, and the usual absence of bilirubin 
at the same time, this form has also been termed " urobilin icterus." 
In this connection it is interesting to note that, according to v. Jaksch, 
bilirubin occurs in the blood in almost every case in which urobilin 
is present in the urine, showing that bile-pigment circulating in the 
blood is in all probability transformed into urobilin in the kidneys. 

Urobilinuria has been observed in certain hepatic diseases; in 
twelve cases of atrophic and hypertrophic cirrhosis examiued, v. 
Jaksch was able to demonstrate the presence of urobilin in the 
urine in every instance, a point which at times may be of consid- 
erable diagnostic importance, providing that other causes which are 
known to lead to urobilinuria can be eliminated. The author has 
observed urobilin in a few cases of hepatic cirrhosis, chronic malaria, 
aud pernicious ansemia, in all of which the skin presented a light 
icteric hue, aud in which bile-pigment was absent from the urine. 
An examination of the blood was, however, unfortunately not made. 
Urobiliu has also been noted in cases of carcinoma, scurvy, Addi- 
son's disease, haemophilia, retro-uterine hsematocele, extra-uterine 
pregnancy, following intracranial hemorrhages, etc. 

Urines which are rich in urobilin usually present a dark-yellow 
color, strongly suggestive of the presence of bilirubin ; the foam 
even in such cases may be colored, making the resemblance between 
the two pigments still more complete, v. Jaksch further points out 
that urines containing indican in large amounts often likewise present 
a very dark-yellow color, a statement with which personal observa- 
tions are in perfect accord. It is possible that the color in such 
cases may be due to the presence of humin-substances derived from 
the indican. In every case a more detailed chemical examination 
should hence be made. The method suggested by v. Jaksch appears 
to be more serviceable than that suggested by Gerhardt. 

v. Jaksch? s lest. 10-20 c.c. of urine are submitted to Huppert's 
test (which see), when in the presence of urobilin in notable quanti- 
ties the precipitate assumes a brownish-red color, which disappears 
upon boiling with acidulated alcohol, the liquid at the same time 
becomiug colored a brownish or pomegranate-red. In the presence 
of only a small amount of the pigment, on the other hand, the liquid 
is colored only a light reddish tinge. 

Gerhardt's test. If the urine contains much urobilin, which the 



444 CLISICAL LIAGXOSI.S 

color will indicate, 10-ii are extracted with chloroform by 

shaking, and the ti:::.:: treated with a few drops of a dilnte solu- 
tion of iodo-potassic iodide. Upon the further addition of a dilute 
solution of sodium hydrate the chloroform extract is colored a yellow 
or yellowish-brown, and exhibits a beautiful green fluorescence 
which is even more intense than that noted in the case of normal 

At times, however, all tests fail and recourse must then be had to 
the spectroscope. la acid solutions urobilin presents a distinct band 

of ao = :-rn:ion :oro r : ■•':_>" :m :1 ■ F." ^mm ' a_ ond"F"to 

the right, while in alkali n r is a n 1 is likewise seen between 

■' and " F." which does nor extend beyond " F." however, and 
is less intense. 

SS \ mm. In case- o: melanotic disease it has been 

repeatedly observed that the urine, which usually and probably 
always presents a normal yellow color when voided, gradually 
becomes darker upon exposure to the air, finally turning black. 
This phenomenon indicates without doubt that such urines contain 
a chromogen, melanogen. which, upon oxidation, yields the black 
pigment noted in these cases, viz., melanin. As yet it has not been 
p"iss:::-l-r to isolate mis sm: -tame m .-m-'st lime : m_.am :::-,a.:::;, 
not definitely determined that the black color in such urines is refer- 
: to one single pigment. Such urines generally contain melanin 
and its chromogen in solution : deposits of melanin granules by them- 
selves are only occasionally seen, a; not at all characteristic, as 
they may alse oe foam I in cases of chronic malarial intoxication. 
etc., when they may, indeed, be met with in the blood, constituting 
spoken of as mdarwBmia. 

AYhile the occurrence of melanin in the urine is probably in 
ti e. in most cases, of the existence of melanotic tumors, it should 
be stated that this symptom cannot be regarded as pathognomonic, 
as it may be absent in the case of melanotic tumors and present in 
w;:st : mi lamasm and inflammatory affections, ana may at times. 
though very rarely, even be associated with the presence of non- 
pigmented growths. Xevertheless, its occurrence should always be 
regarded wtih suspicion, and, taken in conjunction with other symp- 
toms, will often lead to a correct diagnosis. 

Urines which darken upon standing should be subjected tc the 
following tests : 

1. A few urine are treated with bromine-water, when in 



THE URINE. 445 

the presence of melanin or melanogen a precipitate will be obtained 
which is yellow at first and then gradually turns black. 

2. The addition to melanotic urine of a few drops of a strong 
solutiou of perehloride of iron will cause the appearance of a gray 
color, which is imparted to the precipitate of phosphates occurring 
at the time if more of the reagent be added, and which dissolves 
again in an excess. 

Phenol urines. The development of a dark brown or black color 
in urines upon standing is not always due to the presence of melanin, 
as the same appearance may be noted in cases of poisoning with car- 
bolic acid, following the ingestion of salol, hydrochinon, pyrocate- 
chin, and salicylic acid, etc., in large doses. The color in such cases 
is due in all probablityto the presence of various oxidation-products 
of hydrochinon, and in the last instance possibly to the so-called 
humiu-substances. 

The test referred to above will prevent any confusion as to the 
origin of the color noted, as far as melanin is concerned, and with 
the history of the case given, moreover, further chemical examina- 
tion will generally be unnecessary. In suspected cases of carbolic- 
acid poisoning, however, the mineral as well as the conjugate sulphates 

should be quantitatively determined, when the factor (see Sulphates) 

will be found to be greatly diminished. If at the same time other 
factors which might cause a greatly increased elimination of conju- 
gate sulphates can be excluded, the diagnosis of poisoning with car- 
bolic acid, or one of its derivatives, may be inferred. Salol and 
salicylic acid may be recognized from the fact that such urines when 
treated with a solution of perehloride of iron develop a marked 
violet color which does not disappear on standing. The reaction 
thus differs from that obtained with diacetic acid. 

Alkapton. Urines are at times, though very rarely, seen which, as 
those just described, also turn dark on standing, while presenting a 
normal color when voided. A chemical examination will show, 
however, that in these cases melanin as well as hydrochinon and its 
derivatives are absent. The source of the color in such urines has 
been referred to the presence of an aromatic oxyacid, which has been 
variously termed glycosuric acid, uroleucinic acid, urrhodinic acid, 
but which is more commonly spoken of as alkapton. The term 
alkaptonuria, however, is frequently applied to the presence of re- 
lated oxyacids in the urine as well, such as para-oxyphenyl acetic 



416 CLINICAL DIAGNOSIS. 

acid, hydro-para-cumaric acid, para-oxyphenylglycolic acid, oxy- 
amygdalic acid, and homogentisinic acid. Glycosuric acid is more 
frequently seen in children than in adults, its presence being appar- 
ently due to some such metabolic anomaly as the occurrence of cystin 
and diamines in the urine, the condition at times occurring in fami- 
lies and persisting for years. Although it has been found in patho- 
logic conditions, viz., in phthisis, and in one case of brain-tumor, no 
connection appears to exist between any local lesion and the alkap- 
tonuria. Marshall, who was the first to obtain glycosuric acid in a 
pure form, noted a gradually increasing weakness in his case. 

While alkaptonuria is usually a chronic condition, it may also 
occur as an acute disorder. Boraczewski thus found homogentisinic 
acid before death in a case of tuberculosis of the lungs and of the 
peritoneum. As the elimination of indican was much increased in 
this case, and as the ingestion of tyrosin increased the alkaptonuria, 
Boraczewski thinks that the alkaptonuria was referable to an in- 
creased production of tyrosin. 

The presence of such acids may at times give rise to confusion, and 
a case of alkaptonuria may be mistaken for one of glycosuria, if reli- 
ance be placed only upon Fehling's or Trommels test for sugar. 
Several years ago the author had occasion to examine a urine contain- 
ing glycosuric acid, the following note having been made at the 
time: " The urine presents a dark-brown color, which has devel- 
oped on standing. Its reaction is acid; the specific gravity 1.028. 
It reduces Fehling's solution, but does not reduce the subnitrate of 
bismuth, causing merely a blackish discoloration ; the fermentation- 
test is negative. When Ehrlich's test is applied, a dark-brown color 
develops on standing for fifteen minutes, while at the end of an hour 
the urine has turned almost black. " 

For methods of isolating glycosuric acid, see Neubauer and Vogel's 
Urinary Analysis. 

Blue urines. Blue urines are sometimes seen, the blue color being 
due to indigo formed from urinary indican, in all probability, within 
the urinary passages. Their occurrence can be regarded only as a 
medical curiosity. Formerly, when indigo was employed in the 
treatment of epilepsy, blue urines were frequently seeu. At the 
present time, where methylene-blue is occasionally used in the treat- 
ment of malaria and chyluria, the pigment is found in the urine. 

Green urines. Green urines have also been described, the cause 
of the color of which, however, has not been definitely ascertained. 



PLATE XII. 






Ehrlieh's Diazo-Reaetion, as modified by the author. 
The orange color in the lower portion of the test tube may 
be obtained in any urine ; the dark carmine ring indicates 
the presence of the reaction in a well-pronounced degree; 
the colorless zone above is intended to indicate the am- 
monia that has been added. 



THE URINE. 447 

Pigments referable to drugs. Certain drugs may also cause changes 
in the normal color of urine, and in doubtful cases inquiry in this 
direction should be made. It has been pointed out that carbolic 
acid, hydrochinon, pyroeatechin, and salol cause the appearance 
of a dark-brown color, and that after the administration of indigo 
and methvlene-blue blue urines are voided. Santonin, rheum, and 
senna color urines a bright yellow, so that they may resemble 
icteric urines in appearance. The yellow color iu such cases is 
changed to an intense red by the addition of an alkali, and if 
ammouiacal fermentation be going on at the same time in the 
bladder the patient may believe himself to be suffering from hsema- 
turia. The red color thus produced is due to the action of the alkali 
upon chrysophanic acid. When urines containing copaiba are treated 
with hydrochloric acid a red color results, which changes to violet 
upon the application of heat. Daring the administration of potas- 
sium iodide, or the use of iodine in any form, a dark mahogany 
color is obtained when the urine is treated with nitric acid. In 
doubtful cases Stokvis' modification of Jaffe's test for indican 
should be employed, when in the presence of au iodide the chloro- 
form assumes a beautiful rose-red color. 

For the detection of other drugs aud poisons in the urine the 
reader is referred to special works. 

Ehrlich's reaction. In pathologic conditions, and particularly in 
typhoid fever, a chromogen appears to be present in the urine, which, 
when treated with a solution of diazo-benzene-sulphonic acid and 
ammonia, imparts a tint to the urine varying from eosin to a 
deep garnet-red (Plate XII.). This reaction, which is generally 
spoken of as Ehrlich's reaction, or the " diazo-reaction," was at one 
time regarded as pathognomonic of typhoid fever. Subsequent 
researches have shown, however, that it is also at times met with 
in other acute febrile diseases, such as scarlatina, measles, malaria, 
smallpox, pneumonia, etc., and notably in phthisis pulmonalis, in 
which it is frequently observed, and in which its presence for any 
length of time may be regarded as a bad omen. Still there appears 
to be no doubt that its occurrence in doubtful cases may be regarded 
as pointing to typhoid fever, especially when found between the fifth 
and the thirteenth day of the disease, and when it disappears later 
on. The author has studied this question in a large number of 
instances, and has arrived at the conclusion that, while the reaction 
may be observed in other diseases as well as in typhoid fever, it is 



448 CLINICAL DIAGNOSIS. 

usually not difficult to distinguish between these and the latter con- 
dition, excepting in certain cases of acute miliary tuberculosis. As 
the reaction, however, is obtained not later than the twenty-second 
day of the disease, and is usually present as early as the fifth or sixth 
day in typhoid fever, and while it generally does not appear earlier 
than the beginning of the third week, and then persists almost to 
the end in acute tuberculosis, its occurrence may be of decided value 
in diagnosis in many instances. 

Its absence from the fifth to the ninth day in typhoid fever usually 
indicates a very mild case, excepting in children. This rule, how- 
ever, is not an invariable one. The author recently observed a case of 
typhoid fever in which, notwithstanding exceedingly high tempera- 
tures (106.5°), the reaction was not obtained before the beginning 
of the third week, and then persisted for only a few days. 

The author canuot agree with v. Jakscb when he states that he 
" disclaims for this test any clinical importance whatsoever, and 
that he would enjoin the necessity of avoiding inferences based upon 
the appearance of the reaction indicated." Nor does he believe 
that " the color, when obtained, is always due to acetone, and that 
the d'azo-reaction is rather an uncertain indication of that body than 
a test for anything else/' as he has not only been unable to demon- 
strate this reaction in a large number of cases of diabetes in which 
acetone was present, but has likewise only occasionally observed 
acetone in cases of typhoid fever in which a positive result was 
obtained, notwithstanding a most careful examination. 

Since the preparation of chemically pure, crystalline diazo-com- 
pounds is a difficult process, Ehrlich made use of the fact that sul- 
phanilic acid when treated with nitrous acid in a nascent state forms 
diazo-benzene-sulphonic acid, which thus becomes the active prin- 
ciple in the mixture employed. 

Other compounds, of course, can also be used, as the meta-amido- 
benzene-sulphonic acid, the ortho- and para-toluidine-sulphonic acids, 
etc., but of all these Ehrlich found the common sulphanilic acid the 
most convenient. Two solutions kept in separate bottles are em- 
ployed, the one containing 50 c.c. of hydrochloric acid, which is 
diluted to 1000 c.c. and saturated with sulphanilic acid, the other 
being a 0.5 per cent, solution of sodium nitrite. 

To make the test, 40 c.c. of the sulphanilic-acid solution are taken 
in a measuring-glass, and treated with 1 c.c. of the sodium-nitrite solu- 
tion, the mixture being thoroughly shaken. The hydrochloric acid acts 



THE URIJSE. 449 

upon the sodium nitrite, forming nitrous acid, which, in a nascent 
state, forms the diazo-benzeue-sul phonic acid by its action upon the 
sulphauilic acid. Small quantities of the sodium nitrite are used, 
the absence of any free nitrous acid in the mixture being thus in- 
sured ; very small quantities of the diazo-benzene-sulphonic acid are 
at the same time formed, one of the principal requirements in order 
to insure success in the experiment. 

The reaction which takes place is represented as follows : 
I. NaN0 2 + HC1 = NaCl + HN0 2 

.NH 2 
II. C 6 H 4 ( + HN0 2 =C 6 H 4 ( ^N + 2H,0 

Para-amido-benzene-sulphonic Diazo-benzene-sulphonic 

acid. acid. 

In his original article Ehrlich advises the addition of this mixture 
in the proportion of 1 : 1 per volume to the urine to be tested. If 
ammonia be added in excess to the urine thus treated, the color-play 
presently to be described occurs. In a later communication he has 
modified this method by mixing 1 volume of urine with from 5 to 6 
volumes of absolute alcohol previous to the addition of the sulph- 
ani lie-acid mixture, filtering, and then adding the acid mixture to 
the filtrate. 

It is convenient to add about 50 c.c. of absolute alcohol to 10 c.c. 
of urine, to filter, and then to add to the alcoholic urine, which has 
become more or less decolorized, the sulphanilic-acid mixture from a 
burette; 20 c.c. of the latter added to about 30 c.c. of the alcoholic 
urine are sufficient. The addition of the acid in small quantities, 
2 c.c. at a time, for example, followed by thorough shaking of the 
urine, is at times useful, especially in typhoid fever, when the disease 
has advanced to a point at which the color-reaction has no longer its 
original intensity. By the addition of a few drops of ammonia to 
the final mixture the characteristic color appears in typhoidal urine ; 
this, however, disappears on shaking, and becomes permanent only 
after an excess of ammonia has been added. A small Erlenmeyer's 
flask is more convenient for holding the urine than the ordinary 
test-tube, the exact shade being more apparent by transmitted light. 
With this modified method most of the author's experiments were 
performed. 

There is a third method, however, which is more convenient, less 
expensive, and likewise most delicate. A few c.c. of urine are poured 
into a small test-tube, when an equal quantity of the sulphanilic-acid 

29 



450 CLINICAL DIAGSOSIS. 

mixture is added, the whole being thoroughly shaken ; 1 or 2 c.c. of 
ammonia are then allowed to run carefully down the side of the tube, 
forming a colorless zone above the yellow urine containing the acid. 
At the junction of the two a more or less deeply colored ring will 
be seen, the color of which is readily distinguished, the slightest car- 
mine tinge being shown more readily by contrast with the colorless 
zone above and the yellow below, than when dealing with a uniform 
color. If the mixture he then poured into a porcelain basin containing 
water, a salmon-red color will be obtained if the reaction be positive, 
while a yellow or orange color is obtained when negative. This latter 
additional test the author has found most valuable in doubtful cases. 

As to the color-play which takes place in different urines, it will 
be observed that in normal, or pathologic, but non-febrile urines, the 
color of the pure, or alcoholic, urines, when method Xo. 2 is em- 
ployed, remains either unaffected or is merely intensified by the 
addition of the ammonia. A deep orange tint may even be pro- 
duced in this way, but is of no significance whatsoever, and is easily 
distinguished from the typical color. Ehrlich records one exception 
to this rule, namely, that in urines containing biliary coloring- 
matter an intensely dark, cloudy discoloration occurs at times, which, 
upon boiling, is changed to an intense reddish-violet color. 

In the course of certain experiments another very interesting 
exception was met with, but it is to be regretted that there is only 
one observation to record, which the author owes to the kindness of 
Dr. O^den, of Milwaukee. The urine in this case contained a sub- 
stance which reduced Fehling's solution, but did not reduce the 
subnitrate of bismuth, producing merely a black discoloration ; the 
fermentation-test failed completely. Undoubtedly this was one of 
the rare instances in which glyeosurie acid, first isolated by Marshall 
(see above), occurred in the urine. ^Vhen Ehrlich's test was applied 
to this urine according to the second method, a dark-brown color 
developed on standing for fifteen minutes, which at the end of an 
hour turned almost to black. As regards febrile urines, Ehrlich 
observed an intensely yolk-yellow color, which was even imparted 
to the foam when method No. 1 was employed, in rare instances of 
endocarditis ulcerosa, abscesses hepatis, and intermittens; i. e., in 
diseases associated with well-marked chills. 

In tvphoid fever — and this is most important — a color varying 
from that of eosin to a deep garnet develops upon the addition of 
ammonia. Here method Xo. 2, and particularly Xo. 3, were found 



THE URINE. 



451 



very useful, as with these the production of the faintest rose-tint is 
more readily perceived than when No. 1 is employed, owiug to the 
fact that in the second method we are practically dealing with a 
primarily colorless solution, and in No. 3, as above stated, we can 
take advantage of contrasts. 

Greene states that if the solution be prepared, such that one part 
of the sodium nitrite solution is added to 100, instead of the usual 
40 parts of the sulphauilic-acid mixture, a positive reaction is never 
obtained in cases of acute croupous pneumonia and of pulmonary 
tuberculosis. In septic conditions and in cases of advanced malig- 
nant disease, however, a positive reaction may even then be obtained. 
It is possible that the test may be still further modified, so as to 
become truly pathognomonic of typhoid fever. 

The following table is taken from Dr. Greene's very valuable 
paper .- 1 









Cases. 


Plus. 


Minus 


Typhoid fever 10 


10 





Septicaemia 






. 3 





3 


Varicella . 






. 1 





1 


Typhoid relapse 






. 2 


2 





Pseudo-relapse . 






. 1 





1 


Scarlatina 






. 1 





1 


Phthisis pulmonalis . 






. 12 





12 


Lobar pneumonia 






. 3 





3 


Febrile diarrhoeas 






. 2 





2 


Pleurisy . 






2 





2 


Syphilis, second stage 






3 





3 


" third stage . 






2 





2 


Malarial fever . 






2 





2 


Carcinoma, advanced 






. 2 


2 





Chronic rheumatism . 






3 


,0 


3 


Simple anaemia . 






1 





1 


Heart disease . 






4 





4 


Chronic nephritis 






6 





6 


Tuberculosis of hip and e 


Ibow- 


joints 


1 





1 


Arterio-sclerosis 






2 





2 


Cirrhosis of liver 






2 





2 


Oxaluria . 






3 





3 


Gastric ulcer 






1 





1 


Acute bronchitis 






2 





2 


Chronic constipation . 






1 





1 



1 The Diagnostic Value of Ehrlich's Diazo-reaction : Journal of the American Medi call Asso- 
ciation, February, 1894. 



452 CLINICAL DIAGNOSIS. 

Conjugate Sulphates. In addition to indoxyl (see Indican), 
skatoxyl, phenol, paraeresol, and pyrocatechin occur in the urine in 
combination with sulphuric acid. 

Skatoxyl. Skatoxyl results from the skatol formed during the 
process of intestinal putrefaction, as indoxyl is derived from indol, 
and is partly eliminated in the urine as skatoxyl sulphate. Clinic- 
ally it is of little interest, as the amount excreted is very small, and 
it is not necessary here to enter into a further consideration of its 
chemical properties or modes of detection (see Feces). 

Phenol. Phenol, according to Brieger, occurs in only small 
amounts in human urine, the phenol reactions being largely caused 
by paraeresol. ^Normally only about 0.03 gramme is eliminated 
in the twenty-four hours, but in pathologic conditions much larger 
quantities may be found. These conditions are essentially the same 
as those described under Indicanuria, but it should be remembered 
that while an increased elimination of indican is usually associated 
with an increased elimination of phenol, a diminished excretion of 
the former, in those cases in which the increased degree of intestinal 
putrefaction is referable to diseases of the stomach, is never, so far as 
personal observations go, associated with an increased elimination 
of phenol. In cases, however, in which an increased elimination 
of conjugate sulphates is due to albuminous putrefaction going on 
in other parts of the body, as in cases of empyema, pulmonary 
gangrene, putrid bronchitis, etc., an increased elimination of phenol 
alone may be noted, the amount of indican being about normal. A 
greatly increased excretion of conjugate sulphates referable to phenol 
alone is especially observed in cases of poisoning with carbolic acid 
or one of its derivatives ''see also Indicanuria and Sulphates). 

The method employed for the demonstration of phenol in the 
urine is the same as that used for its quantitative estimation. 

Principle : When potassium-phenyl sulphate is treated with hydro- 
chloric acid phenyl sulphate results, which further takes up one mole- 
cule of water, giving rise to the formation of sulphuric acid and 
phenol, according to the following equations : 

/O.CA .O.C 6 H 5 

I. S0 2 < + HC1 = KC1 + SO" 

X OK X OH. 

,O.C 6 H 5 OH 

II. S0 2 ( +H 2 = S0 2 ( -f-C 6 H 5 .OH. 

x OH x OH 



THE URINE. 453 

By the action of bromine- water upon phenol a yellowish-white 
crystalline precipitate of tribromophenol is formed : 
C 6 H 5 .OH + 6Br = 3HBr + C 6 H 2 Br.,.OH. 

As 331 (molecular weight) parts by weight of tribromophenol 
correspond to 94 (molecular weight) parts by weight of phenol, the 
amount of the latter contained in a certain volume of urine is readily 
determined according to the equation : 

331 : 94 : : x : y, and y = ^^ = 0.28398 x, 

in which x indicates the weight of the tribromophenol found in the 
amount of the urine employed, and y the corresponding quantity of 
phenol. 

Method : 500-1000 c.c. of urine are treated with one-fifth of this 
amount of dilute hydrochloric acid and distilled as long as a specimen 
of the distillate is rendered cloudy by the addition of bromine- water 
(1 : 30), the specimens used for this purpose being carefully pre- 
served. The total quantity of the filtered distillate, together with 
the specimens which have been set aside, is now treated with bromine- 
water, shaking the mixture after each addition of the reagent until 
a permauent yellow color results. Beyond this point a further addi- 
tion of bromine-water is beset with danger, as compounds will be 
formed which contain more bromine, the presence of which would 
indicate a smaller amount of phenol than that actually contained in 
the urine. After two or three days the precipitate is collected on a 
filter which has been dried over sulphuric acid, washed with water 
containing a trace of bromine, and then dried over sulphuric acid 
and weighed. The drying over sulphuric acid is necessary, as tribro- 
mophenol is fairly volatile, and a vacuum hence inadmissible. 

Pyrocatechin. Urines containing pyrocatechin, like those con- 
taining hydrochinon (see above), darken upon standing, though pre- 
senting a normal color when voided. For the demonstration of 
these bodies in the urine the reader is referred to special works upon 
urinary analysis. 

Acetone. The amount of acetone which may be found in the 
urine under normal conditions varies between 0.008 and 0.027 
gramme, aud is greatly influenced by the character of the diet. 
Whenever the carbohydrates are withdrawn the quantity rapidly 
increases, and reaches its maximum about the seventh or eighth 
day. At this time from 200 to 700 mgrms. may be eliminated in 



454 CLINICAL DIAGNOSIS. 

the twenty-four hours. If, then, carbohydrates are again added to 
the diet the acetonuria soon disappears. This result is not reached, 
however, if fats are substituted for the carbohydrates. The aceton- 
uria is greatest when but little albuminous food and no carbohydrates 
at all are ingested, and during starvation the same amounts are essen- 
tially found. There can hence be no doubt that acetone is derived 
from proteid material, be this in the form of organized or circulating 
albumin. Increased amounts are accordingly found whenever, as 
in fevers, the various cachexias, in conditions associated with inani- 
tion, etc., large quantities of circulating albumin are broken down, 
or whenever carbohydrates are not furnished in sufficient amount. 

Most important is the diabetic form of acetonuria, and it may be 
stated as a general rule that the diagnosis of diabetes mellitus is justi- 
fiable whenever sugar and notable quantities of acetone are found in 
the urine. The amount of acetone, moreover, stands in a direct 
relation to the intensity of the disease, the maximum excretion being 
usually observed toward the fatal end. Whether or not this form of 
acetonuria can always be explained upon the basis given above must 
still remain an open question. There can be no doubt, however, that 
the threatening symptoms which are so commonly associated with a 
greatly increased elimination of acetone, will often disappear when 
carbohydrates are administered in large amounts. It is certain, 
moreover, that diabetic coma is more apt to occur when the old- 
fashioned plan of excluding carbohydrates entirely from the dietary 
of diabetic patients is adopted. Hirschfeld suggests that in every 
case of diabetes the excretion of acetone be carefully followed, and 
that large amounts of carbohydrates be administered whenever the 
acetonuria approaches a dangerous height. With his experience that 
of the writer agrees entirely. 

Among the febrile diseases in which acetonuria has been observed 
may be mentioned typhoid fever, pneumonia, scarlatina, measles, 
acute miliary tuberculosis, acute articular rheumatism, and septi- 
caemia. In those of short duration, on the other hand, even if the 
fever be high, as in acute tonsillitis, intermittent fever, the hectic 
fever of phthisis, etc., an increased elimination of acetone is rarely 
observed. In the continued fevers the acetonuria is largely refer- 
able to the character of the diet, as carbohydrates are usually excluded 
entirely, and the writer has repeatedly observed that a return to the 
normal occurred as soon as sugar was administered in amounts vary- 
ing from 50 to 100 grammes. 



THE URINE. 455 

In certain nervous and mental diseases, as in general paresis, 
melancholia, following epileptic seizures, and in tabes, acetonuria is 
frequently observed. Daring the second stage of general paresis 
increased amounts are indeed quite constantly found, and Hirsch- 
feld is probably correct when he states that the psychotic form of 
acetonuria is largely referable to improper feeding. 

In the primary diseases of the stomach, and notably in carcinoma, 
acetonuria is quite commonly observed, aud it is possible that the 
acetone in these cases is to some extent, at least, formed in that 
organ directly from the proteids ingested. The fact that in carci- 
noma acetone may be observed at a time when marked loss of flesh 
has not as yet occurred, and that larger amounts of acetone may be 
found in the stomach than in the urine, is certainly in favor of this 
view. 

The acetonuria following chloroform narcosis is probably refer- 
able to an increased destruction of organized albumin. Finally, the 
possibility of the occurrence of an enterogenic form of acetonuria 
must be borne in mind. The cases of so-called asthma acetonicum 
probably belong to this class. 

Tests for Acetone. LegaV s test. This test may be applied to 
the freshly voided urine, but is not conclusive. Several c.c. of urine 
are treated with a few drops of a strong solution of sodium-nitro- 
prusside aud sodium hydrate, when the mixture will present a red 
color, which rapidly disappears, and in the presence of acetone is 
replaced by a purple or violet-red upon the addition of acetic acid. 
As a rule, it is safer to distil the urine (500-1000 c.c.) after the 
addition of a little phosphoric acid (1 gramme pro liter), and to 
employ the first 10-30 c.c. of the distillate for the following tests. 

Ziehen's test. A few c.c. of the distillate are treated with several 
drops of a dilute solution of iodo-potassic iodide and sodium hydrate, 
when in the presence even of traces of acetone a precipitation of iodo- 
form in crystalline form occurs, which may be readily recognized by 
its odor. 

Reynold' s test. A few c.c. of the distillate are treated with a small 
amount of freshly precipitated yellow oxide of mercury. This is pre- 
pared by precipitating a solution of bichloride of mercury with an 
alcoholic solution of sodium hydrate. If acetone be present, a black 
color, due to the formation of sulphide of mercury, will result in the 
clear filtrate upon the addition of a few drops of ammonium sul- 
phide. 



456 CLIXICAL DIAGXOSIS. 

Quantitative estimation of acetone. For the purpose of estimating 

the amount of acetone the method of Messinger, as modified by 

Huppert, is now employed, and greatly to be preferred to the old 
procedure of v. Jaksoh. 

Principle: It is based upon the observation of Lieben that acetone 
gives rise to the formation of iodoform when treated in an alkaline 
solution with iodine. If, thea, a solution of acetone be treated with 
a known amount of iodine, it is a simple matter to determine the 
quantity present by retitrating the iodine which was not used in the 
formation of iodoform. 

Solutions required : 

1. Acetic acid (50 per cent, solution). 

2. Sulphuric acid (12 per cent, solution). 

3. Sodium hydrate solution | 50 per cent. . 

4. A decinormal solution of iodine. 

5. A decinormal solution of sodium thiosulphate. 
Preparation of the solutions : 

1. The decinormal solution of iodine is prepared as described 
elsewhere. 

2. As the molecular weight of sodium thiosulphate — XaoS 2 3 — 
5ELO — is 248, a decinormal solution of the salt would contain 24.8 
grammes to the liter. This quantity is dissolved in about 950 c.c. of 
distilled water, and brought to the proper strength by titrating a 
given volume, such as 10 c.c. with a decinormal solution of iodine. 
A small amount of starch solution is added to the 10 c.c. when 
the iodine solution is added until the blue color has just disap- 
peared. As 1 c.c. of the thiosulphate solution should correspond 
to 1 c.c. of the iodine solution, the necessary amount of water 
which must be added to the former is then determined. 

Method: One hundred c.c of urine, or less, if much acetone be 
present, as determined by Legal's test, are treated with 2 c.c of the 
acetic acid solution and distilled until seven-eighths of the total 
amount have passed over. The distillate is received in a retort which 
is connected with a ball arrangement filled with water. As soon as 
seven-eighths of the urine have been distilled over, a small amount 
of the distillate of the remainder is tested for acetone according to 
Lieben's method. Should a positive reaction be obtained, it will be 
necessary either to repeat the entire process with less urine, diluted 
to about 200 c.c, or to add about 100 c.c of water to the residue 
and to distill until all the acetone has been driven over. The dis- 



THE URINE. 457 

tillate is then treated with 1 c.e. of the sulphuric acid and redistilled. 
The additiou of the acetic acid and of the sulphuric acid, respectively, 
serves the purpose of holding back the phenol and the ammonia. 
Should the first distillate contain nitrous acid, moreover, which may 
be recognized by the addition of a little starch paste containing a 
trace of potassium iodide, when the solution will turn blue, this is 
removed by adding a little urea. The second distillate is received 
in a bottle provided with a well-ground glass stopper, and holding 
about one liter. To prevent the escape of acetone, the glass stopper 
is replaced by a doubly perforated cork, through which two glass 
tubes pass, one to the distilling apparatus, the other to a ball arrange- 
ment, as described above. The distillate is then treated with a care- 
fully measured quantity of the one-tenth normal solution of iodine 
— about 10 c.c. for 100 c.c. of urine — and sodium hydrate solution, 
which should be added drop by drop until the blue color has disap- 
peared and the iodoform separates out. To this end a slight excess 
of the solution must be added. Should ammonia be present, a 
blackish cloud will be observed at the zone of contact of the sodium 
hydrate and the iodine solution, and it will be necessary to repeat 
the entire process. The bottle is closed and shaken for about one 
minute. The solution is then acidified with concentrated hydro- 
chloric acid, when the mixture assumes a brown color if iodine be 
present in excess. If this does not occur, more of the iodine solution 
must be added, and the process repeated until an excess is present. 
The excess is then retitrated with the thiosulphate solution until the 
solution presents a faint-yellow color. A few c.c. of starch solution 
are then added, and the titration continued until the last trace of 
blue has disappeared. The number of c.c. employed in the titra- 
tion is finally deducted from the total amount of the iodine solution 
added and the result multiplied with 0.967. The figure thus obtained 
will then indicate the amount of acetone contained in the 100 c.c. of 
urine, in terms of mgrms., as 1 c.c. of the thiosulphate solution is 
equivalent to 1 c.c. of the iodine solution or to 0.967 mgrm. of 
acetone. 

Diacetic Acid. The occurrence of diacetic acid in the urine must 
always be regarded as abnormal. Its pathologic significance is iden- 
tical with that of acetonuria. It is found especially in diabetes, in 
various forms of digestive disturbance, and in febrile diseases. In 
the high and continued fevers of childhood it is almost constantly 
present. 



458 CLINICAL DIAGNOSIS. 

In order to demonstrate the presence of diacetic acid a few c,c. of 
urine are treated with a strong solution of perchloride of iron, added 
drop by drop. Should a precipitation of phosphates occur, these are 
filtered off, when more of the iron solution is added to the filtrate. 
If now a Bordeaux-red color appears, another portion of the urine 
is boiled and similarly treated. If in the second test no reaction is 
obtained, a third portion of the urine should be treated with sul- 
phuric acid and extracted with ether. A positive reaction, when 
the ethereal extract is tested with perchloride of iron, the color dis- 
appearing upon standing for twenty-four to forty-eight hours, will 
indicate the presence of diacetic acid, particularly if the urine be also 
rich in acetone. 

Oxybutyric Acid. The fact that in some cases of diabetes an 
excessive elimination of ammonia was observed led to the belief that 
there must be present an unknown acid ; this was finally shown to 
be /9-oxybutyric acid. The occurrence of this acid in the urine of 
diabetic patients is of great clinical interest, as a probable connection 
has been established between its presence in the blood and diabetic 
coma. The latter condition is explained by assuming that the diabetic 
patient is unable to furnish sufficient quantities of ammonia to neu- 
tralize the acids formed in the tissues of the body, the alkalies of the 
blood being consequently attacked. A prophylactic treatment with 
alkalies, such as intravenous injections, has hence been suggested in 
severe cases, with an encouraging degree of success. This, however, 
is a mere theory, and the fact that a case of diabetic coma has 
been reported in which the alkalinity of the blood was not dimin- 
ished, and in which recovery took place without the use of alkalies, 
renders the correctness of the hypothesis rather doubtful. Possibly 
the cause of the coma is due to the presence of toxins circulating in 
the blood, causing an increased tissue-destruction, with a simultaneous 
formation of acetone and abnormal acids. 

The presence of oxybutyric acid may always be regarded as indi- 
cating a severe type of the disease, and when associated with marked 
acetouuria and diaceturia as indicating danger of coma. 

The presence of oxy buy trie acid may be inferred in diabetic 
urines if after fermentation a rotation of the plane of polarized 
light to the left be observed. 

Lactic Acid. Sarco-lactic acid is normally absent from the 
urine, but is met with in pathologic conditions, and particularly in 
cases of hepatic disease, the liver normally being concerned in the 



THE URINE. 459 

decomposition of lactic acid and of the lactates that have been 
ingested with the food. 

In order to test for lactic acid the urine is evaporated on a water- 
bath to a thick syrup and extracted with 95 per cent, alcohol. This 
is decanted off after twenty-four hours, evaporated to a syrup, acidi- 
fied with dilute sulphuric acid, and extracted with ether as long as 
this preseuts an acid reaction. The ether is then distilled off, and 
the residue dissolved in water. This solution is treated with a few 
drops of basic acetate of lead, filtered, the excess of lead removed 
by means of sulphuretted hydrogen, and the filtrate evaporated to 
dryness on the water-bath, when the lactic acid will remain behind 
as a slightly yellowish syrup. This is then dissolved in a little 
water, the solution saturated with zinc carbonate, and heat applied. 
Zinc lactate will separate out upon evaporation, and may be recog- 
nized by the form of its crystals, viz., small prisms. 

Volatile Fatty Acids. The term lipaciduria has been applied 
by v. Jaksch to an increased elimination of volatile fatty acids in the 
urine which is observed at times in cases of fever, hepatic diseases 
affecting the proper structure of the liver, leukaemia, both myelogenic 
and lieuo-lymphatic, and in diabetes. Clinically, lipaciduria is of 
no especial significance. Traces of fatty acids are also found under 
normal conditions, and are probably formed in the lower segment 
of the small intestine. The fatty acids which have thus far been 
isolated from the urine are formic, acetic, butyric, and propionic 
acid. They may be demonstrated in the same manner as described 
in the chapter on Feces. 

Fat. Under strictly normal conditions the urine contains no fat, 
while variable amounts may be found in disease. When present in 
large quantities, so that it is possible to recognize it with the naked 
eye, the condition is termed lipuria. Such cases, however, are rare, 
and the diagnosis should only be made when it is possible to exclude 
an accidental contamination of the urine from without. Smaller 
quantities of fat, recognizable only with the microscope, are much 
more common, and are indeed quite constantly observed, whenever 
fatty degeneration of the renal epithelial cells, of pus-corpuscles, or 
of tumor-particles is taking place in the urinary tract. The fat- 
droplets may then be found floating in the urine or attached to or 
imbedded in any morphologic elements that may be present. Lipu- 
ria may also occur when abnormally large quantities of fat are 
circulating in the blood. It is thus observed after the administra- 



460 CLINICAL DIAGNOSIS. 

tion of cod-liver oil in large quantities, following oil inunctions, 
in cases of fracture of the long: bones with extensive destruction 
of the bone-marrow, in cases of eclampsia, as also in such dis- 
eases as diabetes mellitus, chronic alcoholism, phthisis, obesity, leu- 
ksernia, in certain mental diseases, in affections of the pancreas and 
heart, etc. 

The term chyluria or galacturia has been applied to a condition 
in which a turbid urine presenting the macroscopic appearance of 
milk is excreted. Upon microscopic examination it may be demon- 
strated that the turbidity in such cases is owing to the presence of 
innumerable highly refractive globules of fat, which may be removed 
from the urine by shaking with ether. Of morphologic constituents 
leucocytes are occasionally encountered in large numbers. Red 
blood-corpuscles are also seen at times, and when present in large 
numbers impart a rose-color to the urine. Fibrinous coagula are 
often observed when the urine has stood for some time, and the entire 
bulk of urine may even become transformed into a gelatinous mass. 
Albumin is present in most cases in the absence of other constituents 
pointing to renal disease, such as tube-casts and renal epithelial cells. 
Leucin, ty rosin, and cholesterin may at times also be present, par- 
ticularly the latter. It was formerly quite generally accepted that 
this condition was due to the presence of the filaria sanguinis honi- 
inis ; but while filarial are undoubtedly present in the blood in the 
majority of instances, and may also be present in the urine, it has 
been demonstrated that cases occur in which filariasis does not exist, 
and Gotze expressed the opinion that chyluria may be owing to a 
distinct anatomical lesion affecting the renal parenchyma. Further 
observations, however, are necessary, in order to clear up not only 
the etiology of the disease, but also the manner in which fat and 
albumin enter the urine. 

Ferments. Ferments may be demonstrated in every nrine both 
under physiologic and pathologic conditions, but are of little clinical 
importance, excepting, perhaps, pepsin, which is said to be absent 
in cases of typhoid fever, carcinoma of the stomach, and possibly 
also in nephritis. In order to demonstrate its presence a small flake 
of fibrin is placed in the urine, and after several hours removed to a 
2 to 3 p. m. solution of hydrochloric acid. The pepsin, if present, 
will have become deposited upon the fibrin, and cause the digestion 
of the latter in the hydrochloric-acid solution. Diastase, a milk- 



THE URINE. 461 

curdling ferment, and one causing the decomposition of urea into 
carbon dioxide and ammonia have also been observed. 

Gases. Every urine contains a small amount of gases, notably 
carbon dioxide, oxygen, and nitrogen, which may be withdrawn by 
means of an air-pump. In pathologic conditions sulphuretted 
hydrogen is at times also found, constituting the condition known 
as hydrothionuria. It is curious to note in this connection that 
vndigosuria has at times been observed to accompany the hydro- 
thionuria. That the latter condition is the result of bacterial 
activity was shown by Miiller, and the simultaneous occurrence of 
indigo and sulphuretted hydrogen would make it appear that the 
former arises under the same or similar conditions as the latter. 
The occurrence of sulphuretted hydrogen, moreover, is of interest, 
in so far as a retention of the same within the body may exert a 
toxic action. It is not probable that the presence of sulphuretted 
hydrogen is due to an abnormal communication between the gut and 
the urinary passages, and it would appear more likely to be derived 
from the intestinal tract by a process of endosmosis. 

In order to test for sulphuretted hydrogen a strip of filter-paper 
moistened with a solution of subacetate of lead and sodium hydrate 
is suspended to a cork, and the tube or vessel containing the urine 
closed with this, when in the presence of the gas the paper will be 
colored a gray or black. 

Ptomains. Toxic substances of a basic nature are found only 
in traces in normal urines. In pathologic conditions, however, and 
especially in the acute febrile diseases, such as typhoid fever, pneu- 
monia, pleurisy, and acute yellow atrophy, large amounts may be 
found, aud appear to be identical with those obtained from putrefy- 
ing albuminous material. Bouchard pointed out that these sub- 
stances are in all probability formed in the lower portion of the 
intestinal tract. Diamines, viz., putrescin and cadaverin, have been 
found in the urine in cases of cholera Asiatica, pernicious anaemia, 
and in connection with cystinuria. Ptomains in notable amounts 
have also been demonstrated in the urine of maniacs, and the ques- 
tion of autointoxication with substances of this character as an 
etiologic factor in mental diseases is prominently engaging the 
attention of alienists at the present time. The whole subject is 
one of the utmost importance, but, as yet, it must be confessed, 
wrapped in the deepest obscurity. 

In order to demonstrate the presence of ptomains in the urine, 



462 CLIXICAL DIAGXOSIS. 

the methods suggested by Brieger, Stass-Otto, and Gautier may be 
employed, of which the author can recommend that of Gautier par- 
ticularly. 

Sediments. 

In the chapter treating of the general physical characteristics of 
the urine it was stated that on standing every urine gradually be- 
comes cloudy, owing to the development of the so-called nubecula, 
which was shown to consist of a few mucous corpuscles, some pave- 
ment epithelial cells derived from the urinary and genital passages, 
and under certain conditions of a few crystals of uric acid, of oxalate 
of calcium, or both. It was further pointed out that owing to a 
diminution in the acidity of the urine on standing, in consequence 
of an interaction between the neutral urate of sodium and the acid 
phosphate of sodium, a sediment is thrown down which consists of 
acid urate of sodium, and at times of free uric acid (see Reaction). 
Should the reaction of the urine upon being voided be alkaline, how- 
ever, a condition which may occur physiologically, when it is depen- 
dent upon the ingestion of large quantities of vegetables rich in 
organic salts of the alkalies, but which may also be due to ammo- 
niacal fermentation, those constituents of the urine which are held 
in solution merely in consequence of the presence of acid sodium 
phosphate are thrown down. In the latter case the sediment con- 
sists essentially of calcium, magnesium, and ammonium salts. Crys- 
tals of ammonio-magnesium phosphate, it is true, may also be observed 
in alkaline urines of the first variety, but are then almost always due 
to an increased elimination of ammonia, and hence rarely observed in 
physiologic conditions. 

formally calcium is found only in combination with phosphoric 
acid and carbonic acid. Of the three possible calcium salts of 
phosphoric acid—/, e.. Ca 3 ( PO;< 2 , CaBPCX, and Ca(H,P0 4 ) 2 — only 
the former two are found in an alkaline urine, while they may be 
observed also in specimens which are either neutral or at least but 
faintly acid. The acid calcium phosphate, Ca( PLPO^L, is seen but 
rarely in sediments, and its occurrence always presupposes the exist- 
ence of a high degree of acidity, being precipitated together with uric 
acid, and under similar conditions. Calcium carbonate, CaCO ; is 
seen only in neutral or alkaline urines. As soon as ammoniacal 
fermentation has begun, ammonium salts are, of course, formed. 
viz., ammonium urate and ammonio-maguesium phosphate. 



THE URINE. 463 

The following table shows the various mineral constituents which 
are usually observed in sediments, the reaction of the urine being in 
every case the all-important factor: 
Reaction acid. 

Uric acid. 

Urate of sodium. 

Oxalate of calcium. 

Primary calcium phosphate. 

Ammonio-magnesium phosphate. 
Reaction alkaline (referable to fixed alkalies). 

Secondary calcium phosphate. 

Tricalcium phosphate. 

Calcium carbonate. 

Ammonio-magnesium phosphate. 
Reaction alkaline (referable to ammonia). 

Ammonium urate. 

Ammonio-magnesium phosphate. 

Tricalcium phosphate. 

Calcium carbonate. 
In pathologic conditions still other unorganized substances may 
be observed in urinary sediments, viz., cystin, xanthin, tyrosin, 
hippuric acid, indigo, urorubin, bilirubin, hsematoidin, magnesium 
phosphate, calcium sulphate, cholesterin, leucin, tyrosin, fats, ammo- 
nium and magnesium sulphate. Of these cystin, xanthin, hippuric 
acid, tyrosin, calcium sulphate, bilirubin, hsematoidin, magnesium 
phosphate, leucin, and the soaps of magnesium and calcium occur 
only in acid urines, while indigo, urorubin, and cholesterin are 
usually found only in alkaline specimens. Before considering these 
various possible constituents in detail a few words regarding sedi- 
ments in general and the method to be followed in their microscopic 
examination may not be out of place. 

An idea of the nature of a deposit may often be formed by 
simple inspection, especially if the reaction of the urine be known. 

A crystalline sediment, presenting a brick-red color and appearing 
to the naked eye like cayenne pepper, observed at the bottom of the 
vessel, is usually referable to uric acid. On the other hand, a deep 
red, amorphous deposit occurring in an acid urine will consist essen- 
tially of urates, the color in this case, as in the former, being due to 
uroerythrin. Further proof is hardly required. Should any doubt 
be felt, however, it will only be necessary to heat the urine, when 



464 CLINICAL DIAGNOSIS. 

the deposit will be seen to dissolve. A white, flocculent sediment in 
an alkaline urine is usually referable to a mixture of phosphates, 
carbonates, and alkaline urates, and will dissolve without difficulty 
upon the addition of acetic acid, while it remains unaffected by heat. 

A sediment, consisting of pus, occurring in alkaline urines is fre- 
quently mistaken for a phosphatic deposit by the beginner. Aside 
from a microscopic examination this question may be settled by the 
addition of a small piece of caustic soda, and stirring, when in the 
presence of pus the liquid becomes mucilaginous and ropy. If much 
pus be present, a tough, jelly-like mass will be formed, which escapes 
from the vessel en masse when the urine is poured out. Such a 
sediment, moreover, does not disappear upon the addition of an acid, 
and is rendered still more dense upon the application of heat. 

Blood, when present beyond traces, may also be recognized. 

Reliance should, however, not be placed upon the macroscopic 
appearance of a sediment to the exclusion of a careful microscopic 
examination, as those constituents, particularly the morphologic 
elements of a sediment, which are of more especial importance, can 
only be demonstrated in this manner. As a general rule, moreover, 
it may be said that the unorganized elements of a deposit are usually 
of little clinical interest 

Students are frequently in the habit of diagnosing an excessive, 
normal, or subnormal elimination of one or another urinary con- 
stituent from the result of a microscopic examination. This is 
unwarrantable, and it should always be remembered that no con- 
clusions whatsoever can be drawn in this manner as to the amount 
actually eliminated, for nothing would be more erroneous, for ex- 
ample, than to infer an excessive excretion, not to speak of an 
excessive production, of uric acid or oxalic acid from the fact that 
crystals of these substances are seen in large numbers under the 
microscope. Again and again are cases observed in which an exces- 
sive elimination of uric acid, oxalic acid, or phosphates is diagnosed 
by mere inspection, and in which a careful chemical analysis shows 
not only no increase, but even a diminution of the normal quantity. 

A urine which is turbid when passed may be examined micro- 
scopically at once. As a rule, however, it is necessary to wait until 
a sediment has formed. The advice is usually given to allow the 
specimen to settle in a conical glass, to decant off the supernatant 
fluid as soon as a sufficient deposit has been obtained, and to 
examine a drop of the latter upon a slide covered with a cover- 



THE URINE. 465 

glass. This recommendation is a good one, and is usually fol- 
lowed. Not infrequently, however, it is necessary to wait for 
twenty-four hours or even longer, until a sufficient deposit has 
formed ; but even when the urine is kept covered it will frequently 
be found that ammouiacal fermentation has taken place, rendering 
the microscopic examination decidedly unsatisfactory. The urine 
should hence be kept in a clean and well-stoppered bottle until the 
desired deposit has formed. A small amount is then removed by 
means of a clean pipette carried down to the sediment with the 
distal end tightly closed with the finger, care being taken not to 
allow the urine to rush into the tube by suddenly releasing the 
pressure, but withdrawing only a small amount, just sufficient for an 
examination. This is then spread over a clean slide that has been 
moistened upon its surface by the breath, when the specimen may 
be examined at once. Covering the specimen with a slip is not only 
unnecessary, but even undesirable, crushing being thus avoided, while 
at the same time a much larger field is offered to observation at one 
time. A low power of the microscope should always be employed, and 
the high power reserved entirely for more detailed examination. 

MICROSCOPIC EXAMINATION OP THE URINE. 

Of late years the centrifugal machine has been applied to urinary 
examinations, and whenever it is desired to obtain a deposit at 
once, or whenever a deposit separates out so slowly as to endanger 
the integrity of the urine, an apparatus of this kind will be found 
very convenient. Daland's haimatokrit is furnished with an attach- 
ment for this purpose. 

Non-organized Sediments. Sediments occurring in acid 
urines. Uric acid. The form which uric- acid crystals may pre- 
sent in a deposit varies greatly, the most common being the so-called 
whetstone-form shown in Fig. 89. The crystals may occur singly 
or arranged in groups. Accidental impurities, such as threads or 
hairs, are at times covered with such crystals, forming long cylin- 
ders. When presenting this form their presence can generally not 
be determined macroscopically. Very frequently, however, uric 
acid crystallizes out in the form of large rosettes composed of tube- 
shaped or long-pointed crystals, presenting a deep-red color, refer- 
able to uroerythrin, when they are often visible to the naked eye, 
forming the well-known brick-dust sediment at the bottom of the 

30 



466 CLINICAL DIAGNOSIS. 

vessel. While it is generally stated that uric-acid crystals may 
always be recognized by their color, varying from a light yellow to 
a dark brown, the author has repeatedly observed uric acid in sedi- 
ments, in which the crystals, which in such cases formed small 
rhombic plates with rounded edges, occurring singly or several 
joined together, were absolutely devoid of coloring-matter, as far 
as a microscopic examination went (Fig. 99). Uric-acid "dumb- 
bells" are also at times observed, and may be mistaken for calcium 
oxalate. 

Fig. 99. 




Colorless crystals of uric acid. 

A uric-acid sediment is observed in cases in which an increased 
excretion of uric acid occurs, but it should be remembered that, 
as a rule, it is not permissible to infer an increased production or 
elimination from the presence of an abundant deposit of this sub- 
stance alone. Brick-dust sediments are frequently observed in the 
urine during cold weather ; but it would be erroneous to infer an 
increased elimination from such an occurrence, as the phenomenon in 
nine cases out of ten is explained by the fact that uric acid is far less 
soluble in cold than in warm water. Daring the summer months, for 
the same reason, a deposit of uric acid is less frequently observed, 
although an increased amount may nevertheless be present, being 
held in solution owing to the higher temperature. The more con- 
centrated the urine and the more uric acid it contains, the more 
readily will such a deposit occur. Whenever more water is eliminated 
through other channels than is consumed or at least absorbed from 
the intestinal mucosa, such deposits will occur, and are hence noted 
after profuse perspiration, following severe muscular exercise, in 
acute rheumatism with copious diaphoresis, acute gastritis and 
enteritis, profuse diarrhoea, during the crisis of pneumonia, par- 



THE URINE. 467 

ticularly if accompanied by much sweating, etc. In all these con- 
ditions, however, an increased elimination of uric acid does not 
necessarily take place, the all-important factors being the reaction 
of the urine, its degree of concentration, and the surrounding tem- 
perature. On the other hand, uric-acid sediments are frequently 
observed in cases in which uric acid is actually eliminated in 
increased amounts. From what has been said, however, it is clear 
that the occurrence of such deposits is usually not of much diag- 
nostic interest. 

Should formed concretions of uric acid — i. e. , uric-acid gravel — be 
found in the urine, a direct indication is afforded to diminish the 
acidity of the urine and to increase the amount of water, so as to 
guard against the formatiou of a renal or vesical calculus. 

Chemically the nature of a uric-acid sediment may be recognized 
by the fact that the crystals dissolve upon the addition of sodium 
hydrate, reappearing again in the rhombic form upon neutralization 
with hydrochloric acid. When heated with dilute nitric acid the 
beautiful red color of ammonium purpurate is obtained upon the 
subsequent addition of ammonia (murexid test), as described else- 
where (see p. 355). 

Amorphous urates. Sodium and potassium urates frequently, 
especially in fevers, form sediments of such density that upon 
microscopic examination it is almost impossible to discern anything 
but innumerable amorphous granules scattered over the entire 
microscopic field in a most irregular manner, and obscuring all 
other elements that may at the same time be present. Cells or 
casts that might possibly be discovered will frequently be seen to 
be studded with these granules. In such cases it is best to heat the 
urine to a temperature of 50° C, and to filter it as rapidly as pos- 
sible while still hot, the contents of the filter being subsequently 
used for microscopic purposes. 

Urate sediments are always colored, the tint varying from a dirty 
brown to a bright brick-red, owing to the presence of uroerythrin. 
Difficulties can hence never arise in determining the nature of the 
sediment, as a colored deposit appearing in an acid urine, which 
dissolves upon the application of heat, cannot be due to anything 
but urates. If a drop of the sediment, moreover, is treated upon a 
slide with a drop of hydrochloric acid, some characteristic whetstone- 
crystals of uric acid will be seen to separate out, while the greater 
portion will appear in the form of rhombic tablets. 




468 CLINICAL DIAGNOSIS. 

Calcium oxalate. This substance generally appears in urinarv 
sediments in the form of small, colorless, highly refractive octahedra 
(Fig. 100), which vary greatly in size, some appearing as mere specks 
even under a comparatively high magnifying power, while others 
may attain the dimensions of a large leucocyte. Frequently one 
axis is longer than the other. From the fact that their diagonal 

Fig. 100. 

B . # * 

- > z '- '- 
" e » 

i » o 

Less common forms of oxalate of lime crystals. T:>"Layso>~.) 

planes are very highly refractive, apparently dividing the superficial 
plane into four triangles, they have been compared to envelopes, and 
it is this envelope-form of the crystals which is especially character- 
istic. In the same specimen of urine so-called dumb-bell forms may 
be found, which appear to be made up of two bundles of needle-like 
crystals united in the form of the figure 8. The latter, according to 
Beale. originate in the uriniferous tubules, and are frequently found 
adherent to or imbedded in tube-casts. Other forms may also be 
found, and are shown in the accompanying figure. In this con- 
nection the author wishes to draw attention to the occurrence in 
urinary sediments of curious, highly refractive, more or less angular 
bodies, which do not present a well-defined crystalline form, and 
which he is inclined to regard as an amorphous form of calcium 
oxalate. 

While the envelope crystals are highly characteristic and can 
hardly be mistaken for any other substance, the student may at 
times confound them with crystals of ammonio-magnesium phos- 
phate. This error may be avoided if it be remembered that the cal- 
cium oxalate crystals are never so large as those of the magnesium 
salt, and that the latter dissolve upon the addition of acetic acid, in 
which calcium oxalate is insoluble. The distinction from uric acid, 
if we are dealing: with the dumb-bell form, cannot alwavs be made 



THE URIJSE. 



469 



by more inspection. A drop of caustic soda should bo added, which 
will dissolve the crystals if these be uric acid, while calcium oxalate 
remains unchanged. It has been poiuted out that under strictly 
normal conditions a few isolated crystals of calcium oxalate may be 
found in the primitive nubecula, so that their presence in urinary 
sediments cannot be regarded as pathologic. After the ingestion of 
certain vegetables and fruits, notably rhubarb, garlic, asparagus, 
oranges, or following the continued administration of sodium bicar- 
bonate or the salts of vegetable acids, calcium oxalate crystals may 
be observed in large numbers ; so also in certain diseases, such as 
diabetes mellitus, catarrhal jaundice, phthisis, emphysema, etc. 

As in the case of uric acid, no infereuce can be drawn from a 
microscopic examination of the sediment as to the quantity actually 
eliminated. The frequent occurrence of abundant sediments of this 
substance may, however, generally be regarded as abnormal, pro- 
viding that such an occurrence cannot be explained by the nature of 
the diet. It is very suggestive to note the frequency with which 
such sediments are observed in certain cases of neurasthenia, associ- 
ated with a mild degree of albuminuria, as also in various digestive 
neuroses. Finally, as in the case of uric acid, the possibility of the 
formation of renal calculi should be borne in mind whenever abun- 
dant sediments of calcium oxalate are encountered upon frequent 

examinations. 

Fig. 101. 




Various forms of triple phosphates. (Finlayson.) 

Ammonio-magnesium phosphate, usually spoken of as triple phos- 
phate, crystallizes in large prismatic crystals of the rhombic system, 
and is most abundantly observed in alkaline urines, but is also 
epiite f recjuently seen in feebly acid specimens. Of the various forms 
seen, that resembling the lid of a coffin of the old-fashioned type is 



470 



CLINICAL DIAGNOSIS. 



the most characteristic. (Fig. 101.) The size which these crystals 
at times attain is quite considerable ; very small specimens, however, 
also occur which could possibly be mistaken for oxalate of calcium, 
but from which they are readily distinguished by the ease with which 
they dissolve in acetic acid, as has already been pointed out. 



Fig. 102. 




Crystalline phosphates. (Finlayson.) 



Here as elsewhere it should be remembered that no conclusions as 
to the amount actually eliminated can be drawn from a microscopic 
examination, and the diagnosis " Phosphaturia " should only be 
based upon the results of a quantitative anaylsis. 



Fig. 103. 




Monocalcium phosphate crystals. 

Monocalcium phosphate crystals are rarely seen and only in speci- 
mens presenting a highly acid reaction, when uric-acid crystals are 
also frequently observed in large numbers. The author observed 
but three cases of this kind, occurring in patients the subjects of 
functional albuminuria. The urine was highly acid, in one case of 



THE URINE. 471 

a sp. gr. of 1.036, and on standing deposited a sediment which con- 
sisted largely of monocalcium phosphate crystals (Fig. 103), with 
a considerable number of uric-acid crystals, from which they are 
readily distinguished by the absence of pigment and their solubility 
in acetic acid. 

Neutral calcium phosphate, These crystals may be found in alka- 
line, neutral, and feebly acid urines. They are at times of large 
size, but more commonly acicular, occurring either singly or united 
together in a star-like manner (Fig. 102). They are colorless, 
readily soluble in acetic acid, and insoluble in warm water, so that 
they can be easily distinguished from uric acid. 

Basic magnesium phosphate crystals, occurring in the form of 
large, highly refractive plates (Fig. 104), are at times seen in alka- 
line, neutral, or faintly acid and highly concentrated urines. They 
are readily recognized by treating a drop of the sediment upon the 
slide with a drop of ammouium carbonate solution (1 : 4), when the 
crystals become opaque and their edges assume an eroded aspect. 
In acetic acid they dissolve with ease and may then be reprecipitated 
by means of sodium carbonate. 

Fig. 104. 




mM 




Basic phosphate of magnesia crystals, (v. Jaksch.) 

Hippuric-acid crystals have been observed, although rarely, in 
urinary sediments in acute febrile diseases, diabetes, and chorea, 
w^hile their occurrence following the ingestion of large amounts of 
prunes, mulberries, blueberries, or the administration of benzoic acid 
and salicylic acid is more common. 

Hippuric acid occurs in the form of fine needles or rhombic prisms 
and columns, the ends of which terminate in two or four planes, at 
times resembling the crystals of ammonio-magnesium phosphate and 
of uric acid. From the former they may be readily distinguished by 
their insolubility in hydrochloric acid, and from the latter by the 
fact that they do not give the murexid reaction when treated with 
nitric acid and ammonia (see p. 355). In the case of urines rich in 
hippuric acid, in which this does not appear in the sediment, it is 



472 



CLINICAL DIAGNOSIS. 



well to add a small amount of hydrochloric acid, when the crystals 
will gradually separate out. As yet their presence does not appear 
to possess any clinical significance. 

Calcium sulphate in the form of long, colorless needles or elongated 
prismatic tablets (Fig. 105), has been observed in urinary sediments 
in only two cases. In both cases the urine, especially on standing, 
deposited a milky-looking sediment, the reaction being strongly acid. 
It may be recognized by its insolubility in acids and ammonia. 



Fig. 105. 




Calcium sulphate crystals, (v. Jaksch-) 

Cystin, the chemical formula of which is (C 3 H 6 NS0 2 ) 2 , must be 
regarded as an amido-acid, and, according to the observations of 
Baumann, as a normal constituent of the urine. The quantity 
eliminated in the twenty-four hours, however, is very small, 
amounting to not more than 0.01 gramme pro liter. In urinary 
sediments cystin is never found under normal conditions, while 
pathologically its occurrence appears to be intimately associated 
with the simultaneous formation of certain diamines. These, viz., 
putrescin, cadaverin, and a third diamine, isomeric with the latter, 
are formed in the intestinal tract, and are eliminated in the urine 
as well as in the feces. There can be little doubt that the causes 
which give rise to the formation of the one are also responsible for 
the presence of the other, and that the occurrence of cystinuria is thus 
dependent to a large degree at least upon a specific form of intestinal 
putrefaction. Beyond this, however, practically nothing is known of 
the relation existing between these bodies. 

Clinical interest in connection with cystinuria centres in the fre- 
quent association of cystin sediments with cystin gravel or calculi, 
but it is curious to note that the cystinuria, even after removal of 
the calculus, may persist for years without giving rise to symptoms 






the musi:. 



473 



denoting the existence of a pathologic process. Cystin concretions 
and calculi must be regarded as medical curiosities, as not more than 
fifty cases of this kind have been described. 

Urine containing cystin in pathologic amounts may be of normal 
appearance, reaction, odor, and specific gravity, but is often described 
as presenting a yellowish-green color, a higher specific gravity than 
normal, and a curious odor. When undergoing putrefaction a marked 
odor of sulphuretted hydrogen develops, owing to decomposition 
of the cystin. When treated with acetic acid, a white, crystalline 
sediment separates upon standing, which is soluble in ammonia, and 
from which the crystals usually observed in the sediment of the 
native urine may be obtained upon evaporating the ammonia. 

The appearance of these crystals (Fig. 106), which take the form 
of small, colorless, hexagonal plates, and are frequently superim- 
posed upon one another, is quite characteristic. If any doubt exist, 
it should be remembered that uric acid, with certain forms of which 
cystin might possibly be confounded at first sight, gives the murexid 
reaction and is insoluble in hydrochloric and oxalic acids, in which 
cystin dissolves with ease, as also in ammonia, from which the crys- 
tals separate out again upon evaporation, as just described. 

Fig. 106. 




Crystals of cystin spontaneously voided with urine. (Roberts.) 

Cystin crystals, when tested upon platinum foil, burn with a 
bluish-green flame without melting. 

To determine the amount of cystin, the urine should be treated 
with an excess of acetic acid, as directed, and the sediment which 



474 cumejLi l ia 

: :zz> :z «z'z~ _ ^ z.z- - ■" :zz — isi^i — ::"_ - -;:-.-. :: .- '. 
•:.::::: :/ — -z_ '_ . ' T„:> zzr:z : " 1= _ : -■■-. - tZ z > z : - 

ill -_: ;--zz :<i : - Zt ' . :;z: :: := :'-- :z> ::: ; zz ■•.'.: .t 
nric acid be present in the sediment, : he mnsl 

:j ii?.i.:-T:ii' :: iz :n: : Mz zz ni~ : r -ZzziT-r-z :.~ : r-vi; z~> 
;. .:zz^ _r::z:~ is'iir : :" Izzi. 

Laum- cmd tyromm^ which belong to the . : _ - a 

bang represented bj the formulae CfcH^Og and CgH^WOg, re- 
spectively, are never found in the nrine under normal conditions. 
Their presence, indeed, may be regarded as pathognomonic of acute 
yellow atrophy of the liver, excepting, perhaps, some rare cases of 
acute phosphoras-poisoiiing associated with hepatic atrophy, not- 
~ z _ ~ z : _ •;:::_:- :■: : . : 7 : : z : :z : ~z ::;:;: zz z : . w::;: z - - - 
>-::«^:;^ ziij :zV .■- :i:::::::r: :z :z — ~ :: :.: ;zz :e: .-.::: i:::i:" 
due to other causes, in typhoid fever, variola, etc In two cases 
:: ; :- : : ..r .. zi:.__i.:.z: zv ;z: z:--z :z ~z::z ;-. z:>: ::::._" ;. rz^ressiz^ 
:.:.:.:.;• :: :_t \'.t-z ~z- z : :z : . :zr : :zz : : ~i.= ::i":".t:: '::::::::::: 
:: :zesz . : .' . — . z .:~::_?mz :'. z^- :. z::-?: ::;::'\ :.z.: :z t::z:;i- 
zzizi. In ii-Tir-r pzc^phzr-5-1 ::?•: zzzg. zii-r-^ver. '.ii:\z. :z " :; z >5:z 
i : : ; .:-.:.\ : \: : lz : =■ :• :z z: : z : z z i. £zr :z z :: i 1 d z ^z ■>? i= 
z:":':: ~zi= y.zi'.ztir. ;.z: i:z:- j~V.:~ i::;::v :. r :;-•-::- :: 
:z-esi : " r- :_:■■ '; T :t_ : ' -. '. 1= ::'.:;::, :zt :::■:-::■: ::' :zr 1z"t: 
i: ; : : - r . I z z : : : : : - - - - _ r : _ - : i :: * -. z : z z : zz : z - z_:zz f 

in cases of acute yellow atrophy, or present in greatly diminished 
•z:;::. zii i'.rzzij :ezz rzz'crzz: :: — t TzrZ. z. :_r . izi Z: 
rllzz:zir::z :: .ezzlz : / " zz -:„ :.z ::.; =:^i. ;- :: ~T.r zz= " z: 
z^zriei z:: :z"-z= ;z:":z-i^ Z: rr;bz";:lr :::z^z :: z:z:. frizz 
iz::i:-i :■::"«. '::: lis: zz :::zi-z::z :: z:zz, :; i Izrzgz rzz:. z: 
least, in the liver. The albuminous origin of these substances has 
:,'.-: ; z: z::zi s-^r T:zz . 

_z ; zzzz ii zzri-7 -~r: :zz: :z Z: zz.zz: izi :"r:«zz :z".j 
when present in large quantities, the urine in every case should first 
be concentrated upon a water-bath, and examined on cooling. At 
:z:- z;~rTz:.— :z: :zzs- -.::»:zz:z- :zz zrfSrz: iz zzv : z -ziib 
quantities, this procedure may not lead to the desired end, and in 
doubtful cases the following method should be employed : 

The total amount of urine voided in twenty-four hours is precipi- 
tated with basic acetate of lead and filtered, when the filtrate, from 
-z:z:z :.:_r rizi- :: '.mi zzs ":erz rzzzivei :;■• zizzz^s :: sz".: zzz-:zzl 
z'iz:z > t'.'z. ; ;:zt : :: z> ?zii.. i v:l_:zif ^s :::*?::: ".r zi:: St" 



THE URINE. 



475 



aside for crystallization. The residue thus obtained is then micro- 
scopically examined, and if crystals be detected which answer the 
description of tyrosin and leucin, they should be subjected to fur- 
ther chemical tests. 

Tyrosin crystallizes in the form of very fine needles (Fig. 107), 
which are usually grouped together in sheaves or bundles, crossing 
each other at various angle-. They are insoluble in acetic acid, but 
soluble in ammonia and hydrochloric acid. 

Fig. 107. 




Tyrosin crystals. (Charles. 

Leucin (Fig. 108) occurs in the form of spherules of variable size, 
which closely resemble globules of fat, but may be distinguished 
from these by their insolubility in ether. They present a more or 
less pronounced brownish color, and upon close examination con- 
centric striations as well as very fine radiating lines can at times be 
made out, the latter being especially characteristic. 

Fig. 108. 




Crystals of leucin (different forms). (Crystals of creatinin chloride of zinc resemble the 
leucin crystals depicted at a.) The crystals figured toward the right consist of comparatively 
impure leucin. (Charles.) 

If crystals resembling tyrosin and leucin be found, the following 
procedure should be employed : 



476 CLINICAL DIAGNOSIS. 

In order to separate the leucin from the tyrosin, the residue is 
treated with a small amount of alcohol, in which leucin is more 
readily soluble than tyrosin. 

Teds far tyrosin. The sediment is filtered off , washed with water, 
aud dissolved in ammonia, to which a little ammonium carbonate 
has been added. This solution is allowed to evaporate, leaving the 
tyrosin behind. 

Piria's test. A bit of the tyrosin is moistened on a watch-crystal 
with a few drops of concentrated sulphuric acid, covered, and set 
aside for half an hour. It is then diluted with water, heated, and 
while hot saturated with calcium carbonate and filtered. The 
filtrate is colorless, but when heated with a few drops of a very 
dilute solution of perch loride of iron, which must be free from 
hydrochloric acid, it assumes a violet tint (v. Jaksch). 

Hoffmann's test. A small amount of tyrosin, when dissolved in 
hot water and treated, while hot, with mercuric nitrate and potas- 
sium nitrite, imparts to the solution a beautiful dark-red color, and 
yields a voluminous red precipitate. 

Tests for leucin. Seherer's test. To test for leucin, this is sepa- 
rated from tyrosin, as described, by the addition of a little alcohol. 
The alcohol is allowed to evaporate, and a portion of the residue 
treated upon platinum-foil with nitric acid, when a colorless residue 
is obtained, which, upon the application of heat and a few drops of 
a solution of sodium hydrate, forms a droplet of an oily fluid which 
does not adhere to the platinum. 

Hofmeister's test. A small amount of leucin dissolved in water 
cause? a deposit of metallic mercury when heated with mercurous 
nitrate. 

Xanthin crystals (Fig. 109) are very rarely observed in urinary 
sediments, and, as far as can be ascertained, the case observed by 
Bence Jones is the only one on record. Care should be had not to 
confound certain forms of uric acid with xanthin, and the author 
well remembers an instance in which crystals were observed iden- 
tical in appearance with those here pictured, but which upon chem- 
ical examination proved to be uric acid. The necessity of dis- 
regarding the statement generally made that uric-acid crystals found 
rinary sediments are invariably colored cannot be insisted upon too 
strongly. It has been stated elsewhere that colorless uric-acid crys- 
tals may be encountered, and in the case just cited this was observed. 

Clinically, xanthin sediments are of interest only in so far as this 



THE URIXi:. 



477 



Bubstance may give rise to the formation of calculi;' in the case 
observed by Benee Jones attacks of renal colic had occurred several 

years previously. 

Fig. 109. 




r. "3SSW 



H) 



*.*0 



<^ 



a. Crystals of xanthin (Salkowski) ; b. Crystals of cystin (Robin). 

Soaps of lime and magnesia, v. Jaksch has pointed out that in 
various diseases crystals maybe found which "closely" resemble 
tyrosin in appearance, and pictures such crystals (Fig. 110), which 
from their behavior toward reagents he is inclined to regard as 
calcium and magnesium salts of certain higher fatty acids. 

Fig. 110. 




Lime and magnesium soaps, (v. Jaksch.) 



Should any doubt arise, the question may be readily decided by a 
chemical examination (see tests for tyrosin and fatty acids). 

Bilirubin crystals in the form of yellow or ruby-red rhombic plates 
or needles, as well as amorphous granules, have been seen in the 
urine in rare cases, but are of no special interest. They are easily 
soluble in alkalies and chloroform, but not in ether. When treated 



478 CLINICAL DIAGNOSIS. 

upon a slide with a drop of nitric acid, a green ring will be seen to 
form around them (Gmelin's reaction). 

Hcematoidin crystals, which cannot be distinguished from bilirubin 

by the microscope, and also resemble the latter chemically to such a 
degree that Hoppe-Seyler regarded them as practically identical. 
are almost as rarely seen as the former. They may be found either 
free or imbedded within cells or tube-casts in cases of scarlatinal 
nephritis, the nephritis of pregnancy, in granular atrophy and amy- 
loid degeneration of the kidneys, and in carcinoma of the bladder, 
of which latter condition they have been regarded by some as 
pathognomonic. 

It has been stated that haernatoidin crystals may be distinguished 
from bilirubin crystals by the appearance of a transient blue color 
when treated with nitric acid, but v. Jaksch rightly regards this 
reaction as of doubtful value, as a blue color is similarly obtained 
when bile-stained elements of a urinary sediment are treated in this 
manner. 

Fat. M nen small, strongly refractive globules of fat, which 
may be readily recognized by their solubility in ether, are observed 
either floating on top of the urine or held in suspension, it is neces- 
sary to ascertain first of all whether such fat may not have been 
introduced into the urine accidentally, owing to the use of a bottle 
or vessel not absolutely clean, previous catheterization, etc. The 
diagnosis •'"Lipuria" should only be made when all possible pre- 
cautions have been taken to insure against the accidental presence 
of this substance. Every physician who has frequently occasion to 
examine urines has undoubtedly met with instances in which fat- 
globules were found, and in which a careful inquiry showed that 
these were only accidentally present. Lipuria — i. e., an elimination 
of fat usually in the form of minute droplets floating in the urine — 
has been noted in various cachectic conditions, in cases of heart- 
disease, affections of the pancreas and liver, in gangrene, and pyae- 
mia, associated with diseases of the bones, especially fullowing frac- 
tures, in diseases of the joints, etc. Fat has also been observed in 
the urine fullowing the ingestion of large amounts of cod-liver oil 
and inunctions with fats and oils. 

In cases of fatty degeneration of the kidneys, in Bright's disease. 
phosphorus-poisoning, etc., minute droplets of fat are seen in the 
epithelial cells and tube-casts — so minute at times that they appear 
as mere granules. The true nature of these may be recognized by 



THE URINE. 479 

their solubility in ether, benzol, chloroform, carbon bisulphide, 
xylol, etc., and the fact that they are colored black when treated 
with a 0.5 to 1.0 per cent, solution of osmic acid, and red when a 
drop of tincture of alcanna is added to the specimen. The occur- 
rence of fat-droplets in the morphologic elemeuts of a urinary sedi- 
ment should not, however, be regarded as constituting a form of 
lipuria. 

The largest amounts of fat are observed in chyluria, a condition 
which is usually due to the presence of a distinct parasite in the 
blood, the filaria sanguinis hominis, or more rarely the distoma 
haematobium, which has been referred to in the chapter on Blood 
(see Chyluria). 

Sediments Occurring in Alkaline Urines. Basic phos- 
phates of calcium and magnesium. The most common sediments 
observed in alkaline uriues consist of amorphous phosphates of 
calcium and magnesium. They are usually as abundant as the 
urate sediments mentioned, but may be readily distinguished from 
these by the fact that they do not dissolve upon the application of 
heat, but readily disappear upon the addition of acetic acid, and are 
never colored. In this manner it is also easy to distinguish such 
a sediment from one due to pus, with which it might possibly be 
confounded at first sight. Upon microscopic examination a drop of 
the sediment will be seen to contain innumerable transparent granules, 
scattered over the entire field, closely resembling those of urate of 
sodium and potassium. 

Phosphate sediments are observed, as mentioned elsewhere, when- 
ever the reaction of the urine is alkaline, be this owing to the pres- 
ence of fixed alkalies or to ammoniacal fermentation. 

Ammonium urate is only observed in urines which are undergoing 
ammoniacal fermentation. Its presence should always call for a 
careful investigation in order to ascertain whether this has taken 
place after the urine has been voided or before (see Reaction). 

The salt occurs in the form of colored spherical bodies of variable 
size, which are frequently beset with prismatic spicules, and are not 
easily mistaken for any other substance which may be present in 
urinary sediments (Fig. 111). It is characterized, moreover, by its 
solubility in acetic and hydrochloric acids, and the subsequent sepa- 
ration of rhombic crystals of uric acid. 

Magnesium phosphate has been described above (see p. 471). 

Ammonio-magnesium phosphate. While the well-known coffin-lid- 



480 



CLINICAL DIAGNOSIS. 



shaped crystals are commonly seen in feebly acid urines, as pointed 
out, ammonio-magnesium phosphate presents a great variety of forms 
in alkaline urines, especially in specimens undergoing ammoniacal 
fermentation, those resembling flakes of snow being the most com- 
mon (see Fig. 101). 

Fig. 111. 

M 




Ammonium urate crystals. 

Calcium carbonate occurs frequently in alkaline urines, appearing 
under the microscope as minute granules, occurring singly or arranged 
in masses ; dumb-bell forms are also seen (Fig. 112). They may be 
recognized by the fact that they readily dissolve in acetic acid with 
the evolution of gas. 

Fig. 112. 




Calcium carbonate crystals. 

Indigo in the form of delicate blue needles (Plate XIII.), arranged 
in a stellate manner or in plates, visible only with the microscope, is 
rarely seen, and a specimen, such as the one which v. Jaksch pictures, 
can only be regarded as a medical curiosity. In an amorphous con- 
dition, however, indigo may be met with in almost every stale 
urine, occurring in the form of small granules, and frequently stain- 
ing morphologic elements that may be present a distinct blue. Sedi- 



PLATE XIII 




t*- fifth 




Indigo Crystals from a Urine Rich in Indioan, after Standing for Eight Days 
at Ordinary Temperature. (V. Jaksch.) 




THE URINE. 



481 



mints which present a bluish-black color were already noted at the 
time of Hippocrates, and have since been described by numerous 
observers, although the true nature of the coloring-matter has only 
been determined within the last fifty years. Clinically the occur- 
rence of indigo in the urine is of significance only in so far as renal 
calculi have been observed which consisted almost entirely of this 
substance. But little is known of the causes which give rise to the 
appearance of indigo in the urine, but there can be no doubt that its 
occurrence is referable to the action of certain micro-organisms upon 
urinary indican. 

Organized. Constituents of Urinary Sediments. 

Epithelial Cells. (Fig. 113.) Bearing in mind the fact that 
desquamative processes are constantly going on in the epithelial 

Fig. 113. 




Epithelium from the urinary passages. 
a. Round cells ; b, conical and caudate cells ; c, flat cells. 

lining of the various cavities and channels of the body, one should 
expect to find in every urine representatives of the different forms 

31 



482 CLINICAL DIAGNOSIS. 

of epithelium occurring in the urinary organs, from the Malpighian 
tufts down to the meatus urinarius. To a certain extent this actu- 
ally happens, and cells apparently derived from the meatus, the 
urethra, bladder, ureters, and pelvis of the kidneys may be met 
with in almost every specimen, although it may at times be difficult 
to refer the individual cells observed to their proper origin. Bizzo- 
zero even claims that it is impossible to distinguish between the 
cells of the bladder and those of the meatus and renal pelvis, while, 
as a class, they may readily be differentiated in most cases from the 
cells of the urethra, the ureters, the prepuce of the male and the 
vulva and vagina of the female. Cells from the uriniferous tubules 
of the kidneys, on the other hand, are seldom seen in normal urines, 
and when they do occur it is impossible to determine their exact 
origin; i. e., the particular portion of the tubule from which they 
have been detached. Cells presenting the characteristic striated 
appearance seen in the irregular, and to a less evident degree in the 
convoluted portions of the uriniferous tubules, are never observed 
in the urine. This fact, as well as the usual absence of true glan- 
dular cells, remains as yet to be explained. It does not appear 
improbable that the absence of these cells may be referable to a less 
marked degree of desquamation going on in those parts, in which 
the mechanical injury to which the epithelium is subject must of 
necessity be far less severe than in the remaining portions of the 
urinary tract, and particularly in the bladder and urethra. 

As has been stated elsewhere, the number of epithelial cells occur- 
ring in urinary sediments under physiologic conditions is small, and 
the presence of large numbers may hence always be regarded as 
pathologic, indicating the existence of a circulatory or inflammatory 
disturbance affecting some portion of the urinary tract. 

Were it possible in every case to determine the exact origin of the 
cells, it is evident that information of great value could thus be 
obtained, and that it would be a comparatively simple matter to 
localize the lesion. Unfortunately this is not always possible, as the 
form of the cells is dependent to a certain extent upon the reaction 
of the urine, an alkaline or neutral reaction causing the cells to swell 
and to appear larger and rounder than is the case in acid urines. 
As has been mentioned, the cellular type is practically the same in 
the bladder, ureters, and pelvis of the kidneys. 

Definite conclusions should hence be drawn only exceptionally 
from a microscopic examination alone, but there can be no doubt 






THE URINE, 483 

that in conjunction with other factors and the clinical history the 
demonstration of a normal or increased number of epithelial cells 
may frequently be of decided value in a differential diagnosis, and 
taking these factors into consideration it may even be possible to 
localize the seat of the lesion. If attention be directed to the struc- 
ture of the individual cell, and this holds good more especially for 
the cells derived from the uriniferous tubules, an idea may at times 
even be formed of the character of the lesion (see below). 

Ultzmanu recognizes three forms of epithelial cells which may be 
found in urinary sediments, viz.: 

1. Round cells. 

2. Conical and caudate cells. 

3. Flat cells. 

Round cells are usually derived from the uriniferous tubules and 
the deeper layers of the mucous membrane of the pelvis of the kid- 
neys. In the urine they present a more or less rounded form 
and are provided with a distinct nucleus, being not much larger 
than pus-corpuscles, from which latter they may be distinguished 
readily by the presence of a well-defined nucleus, which in pus- 
cells becomes distinct only upon the addition of acetic acid, and, 
moreover, is polymorphous. Whenever such cells are found ad- 
hering to urinary casts, which latter may at times consist entirely 
of these structures, it is clear that they represent the glandular 
elements proper of the kidneys. As similar cells are found in the 
male urethra, some confusion may possibly arise. Should albumin, 
however, be present, the probabilities are that the cells are of renal 
origin. The presence of such cells in large numbers together with 
pus, in the absence of tube-casts and albumin, beyond traces, will 
usually indicate the existence of a simple pyelitis, particularly if 
round cells are found joined together in a shingle-like manner. 
Should the pyelitis be associated with a nephritis, tube-casts and 
albumin in large amouuts will at the same time be present. In 
such cases it may be impossible to determine the origin of the cells, 
excepting of such that may be adhering to tube-casts. In simple 
circulatory disturbances affecting the renal parenchyma no special 
abnormalities can be discovered in the structure of the cells, while 
iu cases of fatty degeneration of the kidneys they will be seen to 
contain fatty particles in greater or less abundance, so that it may 
be possible to determine the existence of degenerative processes 
which may be of inflammatory or non-inflammatory origin. The 



484 CLINICAL DIAGNOSIS. 

same may be said to hold good if the epithelial elements are mark- 
edly granular and occur in fragments. 

Conical and caudate cells are mostly derived from the superficial 
layers of the pelvis of the kidneys, and are hence seen especially 
in cases of pyelitis. Similar cells are also found in the neck of the 
bladder, and may usually be distinguished from those of the pelvis 
by the greater length of their processes. 

Flat cells may come from the ureters, the bladder, the prepuce of 
the male, and the vulva and vagina of the female. These cells pre- 
sent the usual characteristics of squamous epithelium, being large, 
polygonal in form, and provided with a well-defined nucleus, the 
extra- nuclear protoplasm being only slightly granular. Other more 
or less rounded forms are also seen which are derived from the 
deeper layers of the mucosa, but are readily distinguished from 
the small round-cells of the kidneys proper. Irregular or conical 
cells, often provided with one or more protoplasmic processes, like- 
wise come from the lower layer of the mucosa of the bladder and 
ureters. 

While the cells of the bladder may thus be confounded with those 
of the ureters and vagina under the microscope, it is not likely that 
a vaginitis or vulvitis will be mistaken for a cystitis or a ureteritis. 
In doubtful cases specimens of urine should be procured by means 
of the catheter, care first being taken to thoroughly cleanse the vulva. 
The warped appearance so frequently seen in vaginal epithelial cells, 
and the fact that these often and indeed usually appear in masses, 
may further aid in the differential diagnosis. 

It has been pointed out by Peyer that the presence of pavement- 
epithelial cells, together with mucus and leucocytes, in the urine of 
hysterical and anaemic girls may be regarded as indicating an irri- 
tated condition of the genitals, possibly in consequence of masturba- 
tion. Bearing in mind the moist and sensitive condition of the vulva 
of female masturbators, such a view appears plausible. 

A ureteritis, notwithstanding the fact that the ureteral cells closely 
resemble those of the bladder, may be inferred indirectly, the pres- 
ence of squamous cells in abundance pointing to a cystitis, a small 
increase in their number to ureteritis. In conclusion, it should be 
stated that the so-called mucous corpuscles present in every urine 
are nothing more than the youngest vesical cells. 

From what has been said it is clear that, with due precautions and 
taking other factors into consideration, the discovery of epithelial 



Tin: URINE, 485 

cells in large numbers in urinary sediments may be of decided value 
in diagnosis. 

Leucocytes. Leucocytes are only encountered in very small 
numbers in normal urines. A marked increase should, hence, always 
be regarded as indicating the existence of disease somewhere in the 
course of the urinary tract, excepting in females, when their presence 
may be owing to an admixture of leucorrheeal discharge. In the 
latter case the source of the pus will generally be recognized by the 
simultaneous occurrence of pavement-epithelial cells of the vaginal 
type iu correspondingly large numbers. In doubtful cases the urine 
should always be obtained with the catheter, care first being taken 
to thoroughly cleause the vulva. 

Occasionally the pus is derived from a neighboring abscess that 
has opened into the urinary passages. 

The amount of pus found in urines may vary considerably. On 
the one hand, deposits several cm. in height are not at all uncom- 
mon, and closely resemble deposits of phosphates in appearance, for 
w r hich they are indeed frequently mistaken ; on the other hand, it 
may only be possible to discover its presence by means of the micro- 
scope, which should be employed in every case. 

The appearance of the pus-corpuscles likewise varies in different 
cases : In acid urines their form is usually well preserved, and in 
feebly alkaline and neutral specimens it may even be possible to 
observe amoeboid movements when the slide is carefully warmed. 
In alkaline urines, however, . they usually swell up and become 
opaque, so that it is impossible to discern their nuclei unless they 
are treated with acetic acid. At other times, and particularly when 
pus has long remained in the body, as where a neighboring abscess 
has burst into the urinary passages, it may be almost impossible to 
make out a nucleus, and in extreme instances nothing but a mass of 
granular and fatty detritus is encountered. 

While with a certain degree of experience it is hardly likely that 
a distinct sediment of pus will be mistaken for anything else, such 
as a deposit of phosphates, it should be remembered that if pus be 
exposed to the action of ammonia, or an ammonium salt, the pus- 
corpuscles become disintegrated. In such cases, as in cystitis, in 
which ammoniacal decomposition of the urine is taking place in the 
bladder, a deposit may be obtained which macroscopieally resembles 
mucus, and in which pus-corpuscles may not even be demonstrable 
with the microscope. The sediment then escapes as a gelatinous, 



-:- 



: i::~::^.i ;;^ :-v; ;-> 



»-".: :.'r r~ zi«.e "•-:::::::::: i= i : iir :. ::: - :~-_ t>~t. :ni: :_\ :':.-:. 
V:::: •=::"•. :: i ..:: :n= :r: : :.-«t n~=: :«r .:" :: :-t::.i:i :r.rii::tL. :^s*=. 
as a pyuria might otherwise be overlooked. To this end the follow- 
ing procedure, suggested by Yitali, may be employed: 

__t ::.:r. .:,::-: ii.~:i e ' _—_ i;:i:zei ~::i i:^~: :.::::. :« i^:-: 
:i:~. :_t ;:_:ti:> :: : r zl:e: ::t;:t" ~::i : ir~ :":::- :: ::i::i:t :: 
goaiacnm which has been kept from the light, when in the presence 

: ; ■ - :i: - :—- : : -.. := :•:'. . . - ' : i—p :~ir. 

A ; . :.: : i :::::-::::--:: : : :. r _:-. ~ . t tut . : ~~- :. :._ .- ; - ti^riir 




"::-r i": :ii;.z:. 

From a clinical point of view it is most important to establish the 

\\ :--.-. :: :it -;;- :i -rr-.zj :•::..— :: _ 11: = 1:17 ;.: ::r_^ - 

difficult, bat the following data wili be found of great value in a 

z -*■-", ~~ \ Hi;]:;!; ; 

1. In disT^r- ■fleeting the renal urea ?hyma the amount of pas, 
as a rule, is small, except where a large abscess located in the 

£ _t" -::::::. t it: :-tT ..:■« «i im. " .".-: :r_i: :!■= i-rlv]= :: :: r 
kidney. 

In uncomplic 

T_:ic :if z::. : 
rp:^ir":£ :■-!"-. 
same time, and, 

Lei :•: :j:t: .: ..r 
i: iin-'= iipi:- 
:: ;.« :-: ■.::' 
i : :_'■; '-: :: : :.=- 
in: i:-~:c :_/.:. 

t . : i : :• 1 1 i : i 
:i-:: i .: i_ :-: - 



cases it is. a comparatively easy matter to recog- 

:: tie ii*. 2= :_r: :-:iii : iir~:.s. ~:::i 1= :::^. 
especially tube-casts, are usually present at the 
was i bed in the case of renal epithelial cells, 
frequently found adhering to the tube-casts, and 
composing these entirely, when they are spoken 
^asts). In nephritis Bizznzero, the 

usdes stands in a direst relation to the intensity 

:: :ie :.::.:::;. : ::.:■:•-, : - rreitee: i/A:-.- 
i of acute nephritis, while io the chronic forms 
-■"_".-■- i- 11.1.11: "'"it::--: :_ :;: :::::«- ::' i 



THE URINE. 487 

chronic nephritis large numbers of pus-corpuscles appear in the 
urine, they may be regarded as indicating either au acute exacerba- 
tion of the disease or a complicating inflammation of some portion 
of the urinary tract. In such cases errors may be guarded against 
by carefully observing the number and character of the epithelial 
cells present at the same time, when it will often be found that what 
at first sight appears as an acute exacerbation of a chronic process, 
judging from the number of pus-corpuseles, is in reality a secondary 
pyelitis, ureteritis, or cystitis. 

In cases of simple renal hypersemia pus-corpuscles never occur in 
notable numbers. 

2. In pyelitis the amount of pus eliminated may vary consider- 
ably, and at times even perfectly normal uriue may be voided, prob- 
ably owing to the fact that the ureter of the affected side, if the dis- 
ease be unilateral, has become obstructed temporarily, when suddenly 
large quantities may again appear. The diagnosis of pyelitis is often 
difficult, and should be based not only upon the condition of the 
urine, but upon the clinical symptoms, a rule which, of course, holds 
good in other conditions as well. Very significant is the fact that 
the urine in pyelitis is usually acid, a point to be remembered in the 
differential diagnosis between this condition aud cystitis, with which 
pyelitis is quite frequently confounded. A careful examination of 
the epithelial elements present in the urine may also be of value, and 
should never be neglected. Bacteria in large numbers are generally 
present. 

When pyelitis is associated with nephritis it may at times be 
almost impossible to determine the origin of the pus, but if the 
rule set forth above be remembered, that in chronic nephritis the 
number of leucocytes is always small, it is not likely that a pyelitis 
will be overlooked, particularly if the clinical symptoms be taken 
into consideration. 

Matters may become still more complicated when a cystitis is 
accompauied by a pyelitis or a pyelonephritis. Catheterization of 
the ureters, the feasibility of which, even in the male, has been 
clearly demonstrated by the late Dr. James Brown, should be 
resorted to, and it is highly desirable that this most valuable 
method of diagnosis should become common property as soon as 
possible. Fischl regards the presence of cylindrical masses com- 
posed of pus-corpuscles, formed in all probability in the papillary 
ducts, as highly characteristic of pyelitis. Iu the examination of 



488 CLINICAL DIAGNOSIS. 

a number of cases of this kind the author, however, has never been 
able to demonstrate their presence. 

3. A pyuria referable to ureteritis can hardly be diagnosed from 
the appearance of the urine, and in suspected cases catheterization 
of the ureters should be resorted to, which may possibly elicit some 
information of value. 

4. In mild cases of cystitis pus may be altogether absent, while in 
the more severe forms its presence is constant. In cystitis the 
largest amounts of pus referable to disease of the urinary organs are 
observed, exceeded only in those rare conditions in which a neigh- 
boring abscess has suddenly discharged itself through the urinary 
passages. 

As the urine in cystitis is usually alkaline, and always so in the 
more severe forms, the alkalinity being due to ammoniacal fermen- 
tation, it may happen, owing to the disintegrating action of ammo- 
nium carbonate upon the pus-corpuscles, that these may not even 
be demonstrable with the microscope, and that a gelatinous, mucoid 
sediment appears instead, which escapes from the vessel en masse 
when the urine is poured out. Vitali's test for pus (referred to on 
p. 486) should be employed in such cases. 

5. In urethritis pus may be present in the urine in considerable 
amounts. The source of the pus is recognized by the fact that a 
drop may be manually expressed from the urethra, particularly in 
the morning upon awaking. Mucoid gonorrhoeai threads — the 
" Tripperfa'den " of the Germans — which are largely composed 
of pus-corpuscles will almost always be detected in the urine in 
such cases. In order to distinguish between a simple urethritis and 
a urethritis complicated with cystitis, the urine should be obtained 
in two portions aud allowed to settle. In simple urethritis 
affecting the anterior portion of the urethra the first specimen is 
cloudy, while the second one is clear. If the urethritis, how- 
ever, has extended to the neck of the bladder, in the absence of 
cystitis, while the first portion will, of course, be cloudy, the second 
portion may present a variable appearance, being clear at times and 
cloudy at others. This phenomenon is explained by the fact that a 
portion of the pus contained in the posterior portion of the urethra 
has found its way into the bladder. A cystitis may, however, be 
excluded by the acid reaction of the second specimen aud the fact 
that the latter is never so cloudy as the first ; while in cases of 
urethritis complicated with a purulent cystitis the second portion 



THE URINE. 489 

of urine contains at least as much pus as the first, and usually 
more, owing to the pus, which is heavier than the urine, falling to 
the floor of the bladder, in which case also the last drops passed 
will often be found to be pure pus. The reaction of the urine, 
moreover, will then generally be alkaline. 

6. A sudden elimination of large quantities of pus with a urine 
which up to that time has presented a normal or nearly normal 
appearance may almost always be referred to the rupture of a 
neighboring abscess into the urinary passages. Exceptions to this 
rule have been noted in rare instances in which large amounts of 
pus suddenly appeared, the origin of which could not be demon- 
strated upon post-mortem investigation. Whether such a phenom- 
enon, as v. Jaksch suggests, is dependent upon " unusual conditions 
favoring diapedesis" remains an open question. 

Red Blood-corpuscles. The presence of red blood-corpuscles 
in the urine, constituting the coudition usually spoken of as hcema- 
tiiria, is observed only in pathologic conditions, and is, in contradis- 
tinction to hemoglobinuria (which see), a very common occurrence. 

Urine containing blood-corpuscles in notable numbers presents a 
color which may vary from a bright red to a dark brown, verging 
upon black. Upon standing a sediment of a corresponding color is 
obtained in which distinct coagula of variable size are at times seen. 

If the urine should contain but a small number of red corpuscles, 
however, no deviation from its normal appearance will be noted, 
and the diagnosis of hematuria can then only be made with the 
microscope, which should be employed iu every case. The appear- 
ance of the red corpuscles varies greatly, being influenced especially 
by the length of time duriug which they have been exposed to the 
action of the urine. In cases of hematuria of urethral or vesical 
origin it will be found that they have mostly retained their normal 
appearance fairly well, or have become crenated, when they may 
be recognized without difficulty. Other corpuscles, however, will 
probably also be seen which are no longer biconcave, but which 
have become spherical or shruken, and present an irregular outline. 
In cases, on the other hand, iu which the corpuscles have re- 
mained iu the uriue for a longer time, as in hematuria of renal 
origin, the inexperienced will frequently be puzzled by the presence 
of small bodies of the size of red corpuscles, or somewhat smaller, 
which are entirely devoid of coloring-matter, and merely appear as 
faint, transparent rings, often presenting a double contour, and iu 



490 CLINICAL DIAGNOSIS. 

which no nucleus can be discovered. These formations are red blood- 
corpuscles from which the haemoglobin has been dissolved. They 
are usually spoken of as blood-shadows. Chemical tests are rarely 
necessary, but may be employed if any doubt should arise (see p. 
409). 

Cliuically it is, of course, all important to determine the source of 
the blood. This may at times be accomplished without much diffi- 
culty by a urinary examination, but at other times may be almost 
impossible, when the clinical symptoms and physical signs must be 
taken into consideration. 

1. Hematuria of urethral origin, due to urethritis, or traumatism 
incident to catheterization, for example, is a common event, and 
readily diagnosed, as in such cases blood either escapes of its own 
accord from the urethra or may be squeezed out manually. The 
last portions of the urine voided, moreover, will always be found 
free from blood, unless the latter is referable to disease of the neck 
of the bladder, when the blood appears only toward the end of mic- 
turition, or at least more markedly then than in the beginning. 

2. The diagnosis of vesical hsematuria is not always easily made. 
It should be remembered, however, that here the blood-corpuscles 
present a normal appearance, as has been mentioned, unless ammo- 
niacal fermentation is occurring in the bladder, in which case blood- 
shadows are seen in large numbers. The blood, moreover, is less 
intimately mixed with the urine than in cases of renal hsematuria, 
so that the corpuscles rapidly settle after the urine has been 
passed. Blood-clots of an irregular form and considerable dimen- 
sions can only be of vesical origin. A careful examination for the 
presence of any other morphologic constituents which may be observed 
in urinary sediments, considered in conjunction with the clinical symp- 
toms, will usually lead to a correct diagnosis so far as the seat of the 
hemorrhage is concerned. Hsematuria of vesical origin may be due 
to numerous causes, among which may be mentioned diphtheritic 
cystitis, ulcers of the bladder caused by calculi and carcinoma, trau- 
matism, the presence of parasites, and, more rarely, rupture of vari- 
cose veins in the bladder. In determining the cause of the hemor- 
rhage in a given case more reliance should be placed upon the clinical 
history than upon the urinary examination. 

3. In hematuria of ureteral origin characteristic blood-coagula 
corresponding in diameter and form to the ureters are occasionally 
seen. Their presence, however, does not necessarily indicate that 



THE URINE. 491 

the blood has come from the ureters ; more frequently the hemor- 
rhage will be found to be due to disease of the pelvis of the 
kidney. 

4. Tin- diagnosis of hemorrhage into the pelvis of the kidney 
must be based upon the clinical symptoms taken in conjunction with 
the results of a urinary examination. In doubtful cases recourse 
should be had to catheterization of the ureters, when a unilateral 
haematuria may in the majority of cases be regarded as referable to 
this source. 

5. Hematuria of purely renal origin is of common occurrence, 
and may be due to numerous causes, such as a simple hypersemic 
condition of the orgaus, acute nephritis, in which the passage of 
smoky-looking urine containing blood-corpuscles, usually in large 
numbers, is quite a constant symptom, and chronic nephritis, in 
which their number may be taken to indicate the iutensity of the 
morbid process. Hematuria may also be due to renal abscess, 
nephrophthisis, renal carcinoma, and, in rare instances, to aneurism 
and embolism of the reual artery, thrombosis of the renal vein, etc. 
In the malignant forms of the acute infectious diseases, such as 
smallpox, yellow fever, malaria, etc., in scurvy, haemophilia, and 
purpura, iu leukaemia, filariasis, and distomiasis, renal haematuria is 
common. It is also observed in cases of poisoning with turpentine, 
carbolic acid, cantharides, etc. 

6. An idiopathic form of hematuria has also been described, in 
which hemorrhage from the kidueys occurs without apparent cause. 
To this form Senator has applied the term " renal haemophilia." 
The writer has seen three cases of this kind in which no lesion 
existed which could be made responsible for the hemorrhage. In 
all three the attacks of haematuria were invariably associated with 
anachlorhydria, while normal values were found between the attacks. 
Two of the patients were males and undoubtedly neurasthenics. The 
third was a hysterical chlorotic female, in which haematemesis, pul- 
monary hemorrhages, and melaena were also at times observed. 

Haematuria of renal origin is usually recognized without much 
difficulty, as iu such cases tube-casts, bearing red blood-corpuscles, 
aud at times apparently consisting of these altogether, as well as 
numbers of renal epithelial cells, will usually be found upon careful 
examination. The blood, moreover, is intimately mixed with the 
urine, aud the individual corpuscles have mostly lost their haemo- 
globin and appear as mere shadows. The clinical history should, of 



CLINICAL DIAGNOSIS. 

coarse, always be taken into consideration, and especially in deter- 
mining the primary cause of the hemorrhage. 

Urine containing red blood-corpuscles is always albuminous, so 
that it may sometimes be difficult to decide in a given case whether 
the albumin found is due solely to the presence of blood, or 
whether the hematuria is complicated with an albuminuria per se. 
Frequently it is possible to arrive at some conclusion by comparing 
the amount of albumin with the number of red corpuscles, the 
presence of a large amount of the former in the presence of only a 
small number of the latter indicating that the albumin is not alto- 
gether due to the blood. At other times it is impossible to gain 
information in this manner, when the only expedient left is to de- 
termine the quantity of albumin and of iron separately, and to ascer- 
tain whether the amount of iron found is sufficient to combine with 
that of the albumin. As a rule, however, the presence of serum- 
albumin, aside from that contained in the blood of the urine, may 
be inferred whenever tube-casts are present, although the amount can 
only be estimated approximately in this manner. 

Tube-casts. In various pathologic conditions, and it is claimed 
even in health, curious formations are seen in the urine, which repre- 
sent moulds of different portions of the uriuiferous tubules. To 
these the term tube-casts or urinary cylinders has been applied, and 
it may be said that there is hardly a subject of greater importance in 
urinary analysis, from a clinical point of view, than that of eylia- 
druria ; but it must also be admitted that notwithstanding numerous 
investigations our knowledge of their nature and mode of formation 
is still defective, and the same may be said of their clinical signifi- 
cance. The term li tube-casts/ 7 however, is not altogether appro- 
priate, as it is only applicable to one great division of such forma- 
tions — i. «?.. to those consisting of a uniform, transparent, gelatinous 
matrix to which other elements, such as epithelial cells, red blood- 
corpuscles, leucocytes, and salts in a crystalline or amorphous form, 
may accidentally have become attached — the tube-casts proper. 

From these what may be termed ;; pseudo-easts " must be sharply 
differentiated, a pseudo-cast being characterized essentially by the 
absence of a uniform matrix. Closely related apparently to the 
true cast are the so-called cylindroids — band-like formations which 
resemble the former in appearance, and like these may carry various 
morphologic elements as well as salts. It is thus necessary to dis- 
tinguish between true casts, pseudo-casts, and cylindroids. Of these 



THE URINE. 493 

the true casts are by far the most important and the most common. 
They may be divided into hyaline and waxy casts, the two forms 
being- readily differentiated by the fact that the former readily dis- 
solve in acetic acid, while the waxy casts are either not affected at 
all by this reagent, or, if so, at least not so rapidly. The latter, 
moreover, are more strongly refractive, to which property their 
waxy appearance is owing; their color is slightly yellow or yel- 
lowish-gray, while the hyaline casts are colorless and usually very 
pale and transparent. 

Before giving a detailed description of these various forms it may 
not be out of place to consider briefly the mode of examination that 
should be employed. 

As tube-casts readily undergo disintegration within a compara- 
tively short time in urines containing bacteria even in moderate 
numbers, a microscopic examination should be made as soon as pos- 
sible after the urine has been voided — i. e., as soon as a sufficient 
sediment has formed. The examination should never be delayed 
longer than twelve hours, unless some antiseptic substance has beeu 
added. For this purpose chloroform- water (5-7.5 grammes pro 
liter) is the most convenient, according to Salkowski, of which 20 
to 30 c.c. should be used for every 100 c.c. of urine. The use of 
the centrifugal machine is, of course, best of all, as a sediment suffi- 
cient for microscopic purposes may be obtained in a few minutes. 
In the text-books on urinary analysis mention is usually made of 
the difficulty attending the search for hyaline casts, owing to their 
transparency, and the advice is usually given to color the prepara- 
tion with a drop of a dilute solution of iodo-potassic iodide, or of 
some other staining reagent, such as gentian-violet, picrocarmiu, 
methylene-blue, or osmic acid. In the case of the inexperienced it 
is possible that such a procedure may at times be of value, but, as a 
rule, it may be doubted whether a student who has been unable to 
find tube-casts, if the procedure which has been described above 
be employed — i. e., careful examination, without a cover-glass and 
with a low power, of a drop of the sediment carefully spread over a 
slide — will be materially aided by the use of stains. With a high 
power of the microscope, it is true that tube-casts may be overlooked 
again and again, not only by the student, but also by those familiar 
with clinical microscopy: a high power should, as a ride, only be 
employed to study details of structure. 

True casts. 1. Hyaline casts. (Fig. 114.) Upon careful exami- 



494 



CLINICAL DIAGNOSIS. 



nation it will be seen that with rare exceptions the matrix of hyaline 
casts is not altogether homogeneous, as small granules may almost 
always be detected imbedded in or adhering to the matrix. As 
these granules may occur in greater or less numbers, hyaline casts 



Fig. 114. 




■***%. 



Hyaline tube-casts. 



are spoken of as being fiuely granular (Fig. 115), coarsely granular, 
finely dotted, etc. Should true morphologic elements be detected, 
the casts are termed blood-casts, epithelial casts (Fig. 116), or pus- 



FlG. 115. 




Granular tube-casts. 



casts (Fig. 117). It would be better, however, to add the term 
hyaline in every instance, so as to distinguish them from pseudo- 
casts, which consist of three elements entirely, and lack a uniform 



THE URINE. 



495 



matrix. It would thus be proper to speak of hyaline epithelial 
casts, hyaline blood-casts, etc., and to apply the collective term — 
compouud hyaline casts — to these various sub varieties. 



Fig. 116. 




The true nature of these various forms can probably always be 
made out without much difficulty, and even in those cases in which 
the hyaline matrix is apparently concealed beneath cellular elements 
it will usually be possible upon closer observation to detect a fine 
boundary-liue at some portion of the structure. Not infrequently 
the end of the cast will be seen to be more or less distinctly hyaline. 

Fig. 117. 




Pus casts. 

In others, again, a hyaline zone may be observed along the sides 
of a central organized thread, so to speak, this being frequently 
seen in specimens which are very broad and long. Should any 
doubt, however, arise, a drop of acetic acid is added to a drop of 
the sediment on the slide; the acid dissolves the hyaline matrix, the 
organized constituents are set free, and the differential diagnosis 
between a pseudo-cast and a compound hyaline cast is thus readily 
established. 

The length of hyaline casts may vary greatly. It may scarcely 



496 



CLIXICAL DIAGXOSIS. 



exceed the breadth, on the one band, while on the other, although 
rarely, it may pass through the entire microscopic field. In breadth 
they vary between 0.01 and 0.05 mm. As a rule, the breadth of a 
cast is uniform throughout its entire length, but specimens are not 
infrequently observed in wkii'h one end tapers off considerably, and 
presents a spirally twisted appearance. This may be so marked that 
the entire cast appears transversely striated. It is generally sup- 
■ jsed that this results from the adhesion of one end of the cast to 
the walls of a tubule the lumen of which it does not fill, the free 
end becoming twisted in the downward course. A dichotomous 
branching; of one end is also at times seen in verv Inroad hyaline 



specimens. 



Fig. 118. 




a. Fatty casts, o and e. Blood-casts, d. Free fatty molecules. (Robeets. j 



" Fatty globules are fouud upon the surface of granular casts 
Fig. 11 v . but they also form by themselves short, strongly refrac- 
tive casts, which are often beset all over with needles of fatty crys- 
tals. These, however, are not composed exclusively of fat. but 
probably to some extent of lime and magnesium salts of the higher 
fatty acids and allied cnrnpounds. for they are not all soluble in 
ether. They have their origin doubtless in fatty degeneration of 
the renal epithelium" ; v. Jaksch). 

Granules of melanin, indigo, and altered blood-pigment may also 
at time served in casts; Riedel regards the occurrence of dark 

brown casts as pathognomonic of fractures. 



THE URINE. 



497 



Fig. 119. 




2. The waxy casts (Fig. 119) may be divided into two groups — 
true waxy casts and amyloid casts ; but as the latter are not neces- 
sarily indicative of the existence of amyloid degeneration of the 
kidneys, such a classification is at the present 
time at least of only theoretical interest. They 
are readily distinguished from the hyaline 
casts by the characteristics mentioned above 
— i. c, their higher degree of refraction, 
their yellow or yellowish-gray color, and 
the fact that they are either not attacked at 
all by acetic acid or only very gradually. 
As a rule, only small fragments are found, 
but these are broader and stouter thau the 
stoutest hyaline casts. Waxy casts may also 
contain cellular elements, crystals, and amor- 
phous mineral matter ; but, as a rule, such 
compound casts are not so frequently ob- 
served as are those of the hyaline variety. 
From the latter they differ furthermore in 
frequently presenting a cloudy appearance, 
which in some cases is undoubtedly due to 
the presence of innumerable bacteria, and it 
has been suggested that these may be directly 
concerned in their production. 

As has just been stated, some waxy casts tals of oxalate of lime. c. 

^ , ., ,. . l7 Fragments of waxy casts, (v. 

give the amyloid reaction ; i. <?., they assume j AKS ch.) 
a mahogany color when treated with a dilute 

solution of iodo-potassic iodide, which turns to a dirty violet upon 
the addition of dilute sulphuric acid. It should be remembered, 
however, that this reaction in casts does not necessarily indicate the 
existence of amyloid disease of the kidneys, as the reaction may be 
absent on the one hand in this condition, and present ou the other 
where amyloid degeneration does not exist. This curious phenom- 
enon is usually explained by assuming that such casts have remained 
in the uriniferous tubules for a long time, and have there undergone 
certain chemical changes analogous to the so-called " amyloid meta- 
morphosis" of old precipitates of fibrin, and it is indeed possible 
that waxy casts are originally hyaline. Frerichs has pointed out 
that fibrin which has remained in the uriniferous tubules for a long 
time becomes denser and yellowish in appearance, which would 

32 




Different forms of waxy casts : 

With a coating of urates, b. 

Waxy cast covered with crys- 



4 • - CLINICAL DIAGNOSIS. 

explain the fact that these casts are only with difficulty attacked 
by acetic acid. 

Before leaving tins subject it should be stated that "cast-like" 
formations, consisting entirely of amorphous urates, are not infre- 
quently encountered in urines, and according to Leube they may 
be obtained from any urine, if it be concentrated in a vacuum at a 
temperature of 37° to 39 Q ^rudents frequently regard such for- 
mations as coarsely granular casts, an error which may be guarded 
against if the characteristics of hyaline casts set forth above be 
borne in mind. 

Bacteria (in cases of infectious pyelo-nephritis), ha?matoidin, and 
granular detritus frequently occur grouped in a cast-like manner ; 
their nature is readily ascertained, as in the case of the so-called 
:.:■:..-.- ::.-:- : :.~: dr5:r:::r:;. 

Pseudo-casts, consisting of epithelial cells or blood-corpuscles and 
fibrin, are rarely seen in urinary sediments. The epithelial pseudo 
casts are probably only seen in cases of desquamative nephritis, and, 
unlike the true casts, are hollow, the epithelium of the uriniferous 
tubules being thrown off en masse. Blood-casts (Fig. 118) consist 
of fibrin, within the meshes of which red corpuscles, presenting either 
a normal appearance or occurring as mere shadows, owing to the 
fact that their haemoglobin has been dissolved out, will generally 
be found. They are found whenever extensive hemorrhage has 
taken place in the renal parenchyma, and are far more frequently 
seen than the epithelial pseudo-casts. Hyaline casts are probably 
always met with in urinary sediments in which pseudo-casts are 
found, and may be readily distinguished from the latter, even 
when beset with numerous epithelial cells or red corpuscles (see 
above). 

Gylindroias (Fig. 120) resemble hyaline tube-casts somewhat in 
general appearance, but differ from them in being much larger and 
band-like. Like tube-casts, they have a uniform breadth, and 
are often beset with crystals and cellular elements, such as leuco- 
cytes, red corpuscles, and epithelial cells. They are easily dissolved 
by acetic acid, thus differing from the mucous cylinders or pseudo- 
cylinders (Fig. 121), which may be observed in any urine containing 
mucus in abundance ; the latter probably never contain morphologic 
or mineral constituents, and are never of the same breadth throughout 
their length. The cylindroids proper are undoubtedly of renal origin 
and closely related to the true casts; formations are indeed not 



THE UlilM-:. 



499 



infrequently seen in which a tube-cast terminates in a cylindroid at 
one or both ends (see Fig. 114). 



Fig. 120. 




a and b. Cylindroids from the urine in 
congested kidney, (v. Jaksch.) 



Fig. 121. 



Mucous cylinders. 



Formation of Tube-casts. Several hypotheses have been ad- 
vanced to explain the formation of tube-casts — reference is here only 
had to true casts, and not to pseudo-casts, the origin of which is suffi- 
ciently obvious — and until recently it was quite generally accepted 
that these consisted of coagulated albumin which had transuded into 
the tubules; according to this view a cylindruria would always be 
indicative of the existence of albuminuria. In Neubauer and VogePs 
Urinary Analysis, latest edition (ninth), it is stated that " as to the 



500 CLINICAL DIAGNOSIS. 

significance of tube-casts it must be remembered that these, according 
to our present knowledge, consist of albumin, which coagulates under 
the influence of the acid reaction of the urine in the renal paren- 
chyma in a peculiar hyaline manner. They merely represent a 
solidified portion of the albumin held in solution by the urine ; their 
elimination essentially indicates the existence of an albuminuria." 

More recently, however, probably owing to the reported absence 
of albumin in certain cases of cylindruria, it has been suggested that 
tube-casts are the product of a faulty metamorphosis, or of inflam- 
matory irritation of the renal epithelium, and that a secretion from 
these cells or a disintegration of their protoplasm occurs, resulting 
in the formation of cylindroids or true casts. As far as the exist- 
ence of a cylindruria sine albuminuria is concerned, the author must 
confess that he is very skeptical as to the actual occurrence of such 
a condition, and he fully agrees with Neubauer and Vogel when 
they state that " whenever the number of tube-casts is minimal the 
corresponding amount of albumin may be so insignificant that it may 
not be demonstrable by means of the ordinary, coarser tests." In 
several thousand examinations a true case of cylindruria sine albu- 
minuria has never been observed by the writer. It is difficult, more- 
over, to imagine that an elimination of blood-casts and others, which, 
according to Kossler, are " frequently" encountered in urines, can 
take place in the absence of a coincident elimination of albumin, as 
is claimed by him, and until further and more convincing evidence is 
offered in favor of a cellular origin of tube-casts, it may be better to be 
conservative and to regard cylindruria as equivalent to albuminuria. 

Clixical Significance of Tube-casts. Formerly the occur- 
rence of tube-casts in the urine was held to indicate the existence of 
nephritis. This view has been abandoned, however, for the same 
reasons which led to the rejection of the theory that albuminuria 
invariably indicates Bright's disease (see above). 

The statement is frequently made in text-books that tube-casts 
mav occur in the urine of perfectly healthy individuals following 
severe muscular exercise, cold baths, etc. — in short, all stimuli which 
may cause the appearance of albumin in apparently normal indi- 
viduals. It has been indicated elsewhere (see Functional Albumin- 
uria), however, that such stimuli should not be regarded as " physio- 
logic" in every instance, and the presence of tube-casts in the urine 
similarly should be regarded as a pathologic event. 

It is not necessary in this connection to enumerate the various 



THE URINE. 501 

pathologic conditions in which cylindruria is observed, these being 
the same as those which give rise to albuminuria; and just as a 
nephrangiogenic albuminuria is more frequently observed than a 
nephriHdogenic albuminuria, so also is the presence of tube-casts in 
the urine more frequently due to circulatory disturbances in the 
kidneys than to true nephritis. In every case in which tube-casts 
occur iu the urine it may be assumed that the accompanying albu- 
minuria is, to a certain extent at least, of renal origin. 

While the existence of cylindruria is not necessarily associated 
with definite pathologic alterations of the renal parenchyma, this 
statement should be restricted to the occurrence of purely hyaline 
casts when present in only small numbers. A few renal epithelial cells 
may be found at the same time, occurring either free in the urine 
or adhering to the casts, but never presenting an atrophic or other- 
wise altered appearance in the absence of definite renal lesions. The 
presence of compound hyaline and coarsely grauular casts, as well as 
of waxy and amyloid casts, on the other hand, may probably always 
be regarded as indicating definite changes in structure, so that, so far 
as the diagnosis of nephritis is concerned, a microscopic examination 
of the urine will furnish information far more valuable than the 
simple demonstration of albumin. 

Hyaline casts are those most usually seen — reference is here had 
only to the purely hyaline or, at least, but faintly granular form — 
and are found in all conditions in which albuminuria occurs. When 
preseut in only small numbers, and particularly when occurring but 
temporarily in the urine, it may be assumed, in the absence of other 
symptoms pointing to renal disease, that we are dealing with a 
mild circulatory disturbance in the kidneys. Renal epithelial cells 
are absent, or, if present, they are seen in only small numbers 
and present no special alterations in structure. The albumin- 
uria at the same time is only trifling. If, however, hyaline casts 
be continuously present in large numbers, and if the amount of 
albumin exceed a trace, the existence of a nephritis may usually be 
inferred. Iu such cases granular casts and compound hyaline casts, 
particularly the former, will usually also be found, if the nephritis 
be chronic, while in the acute form the hyaline type will prevail. 
Should blood-casts be present at the same time, the probabilities are 
that we are dealing with an acute nephritis, or an acute exacerbation 
of a chronic process, in which latter case, however, coarsely grauular 
casts will also be present in large numbers. 



502 CLINICAL DIAGNOSIS. 

Waxy casts always indicate a chronic or, at least, a subacute pro- 
cess. The fatty casts described by Kuoll aud v. Jaksch " are most 
commonly associated with subacute or chronic inflammations of the 
kidney of protracted course, with a tendency to fatty degeneration of 
the renal tissues. Post-mortem examination has shown that they 
form most frequently in cases of large white kidney. In some cases 
in which they were present, however, the organ was found to be 
more or less contracted ; but when this was so, it was invariably 
far advanced in fatty degeneration." 

It has been stated that from a careful examination of the renal 
epithelial cells it is often possible to determine whether an inflam- 
matory process affecting the kidneys is at the same time complicated 
with degenerative changes. As a matter of fact, the cells found on 
the tube-casts under such conditions no longer present a normal 
appearance, but are shrunken and atrophied, and in cases of fatty 
degeneration of the kidneys studded with fatty granules. Epithelial 
casts, in the absence of distinct changes affecting the renal paren- 
chyma, are probably never seen. 

The occurrence of pus-casts presupposes the existence of suppura- 
tive inflammation in the kidneys, while the presence of only a small 
number of leucocytes on hyaline casts may be observed in the ordi- 
nary forms of nephritis aud particularly in the acute form. 

The pathologic significance of the so-called amyloid casts and 
pseudo-casts has already been considered. 

Cylindroids are present whenever hyaline casts are seen in the 
urine, and have essentially the same import. They are said to occur 
most frequently in the urine of children. 

So far as the constancy with which tube-casts occur in the urine 
in nephritis is concerned, it is well known that in the chronic inter- 
stitial form of the disease they, as well as albumin, are frequently 
absent for a long time, so that it may only be possible to make the 
diagnosis from the clinical history and the physical signs. It is a 
well-known fact, moreover, that pathologic alterations of the kid- 
neys, particularly in men past middle-age, are observed again aud 
again in the post-mortem room, where a previous examination of the 
urine showed no evidence of the existence of renal disease. In 
the acute and subacute forms of nephritis as well as in the ordi- 
nary parenchymatous form, tube-casts are probably always found, 
and it would further appear that acute circulatory disturbances 



THE URINE. 



503 



affecting the renal parenchyma quite constantly lead not only to 
albuminuria, but also to cylindruria. 

Spermatoza. Spermatozoa, for a description of which the reader 
is referred to the chapter on Semen, are frequently observed in the 



Fig. 122. 




Human spermatozoa. 

urines of healthy adults, and are quite constantly met with in 
the first urine passed after coitus or pollutions, when their pres- 
ence is, of course, of no significance. (Fig. 122.) Such urines are 
always cloudy, but it is impossible to recognize the source of the 
turbidity by simple inspection. 

A sediment composed of phosphates is popularly regarded as 
being due to semen, and no doubt every physician has seen patients 
— usually sexual neurasthenics — who were greatly alarmed at finding 
a white deposit in the chamber, and who imagined themselves " suf- 
ferers from loss of manhood. " The microscope is necessary in every 
case to determine the presence of spermatozoa. 

In females semen is found in the urine whenever the external 
genitals have been polluted during or after coitus as well as in the 
exceptional cases in which connection has been effected by the 
urethra. From a medico-legal standpoint the discovery of sperma- 
tozoa in the urine of women may be of the greatest importance, but 
otherwise is without significance. 

In a few instances it is stated that trichomonades have been mis- 
taken for spermatozoa. The writer, however, is convinced that such 



504 CLINICAL DIAGNOSIS. 

an error could only occur if the observer is totally unacquainted with 
questions appertaining to microscopic research. 

In pathologic conditions spermatozoa are not infrequently found 
in the urine. In cases of severe constipation, owing to pressure 
of the hard scybalse upon the seminal vesicles, a partial evacuation 
of semen may occur, which may or may not be accompanied by a 
certain degree of sexual excitement. Horowitz has pointed out that 
a discharge of semen may be noted in cases of periurethral abscess 
with perforation into the ejaculatory ducts, giving rise to spermato- 
cy-stitis, the condition being due to a tight stricture of the urethra 
with dilatation beyond the constricted portion. The author observed 
a case of cystitis in which spermatozoa could almost always be de- 
tected in the urine. An operation revealed a tight stricture of the 
urethra and a sacculated bladder ; the constant elimination of semen 
was apparently owing to the irritating action of the atnmoniaeal 
urine. It should be noted that in this case, as well as in those in 
which semen is frequently passed during the act of defecation in the 
absence of sexual excitement, no deleterious effects referable to such 
loss were noted. In the urine voided during or after epileptic and, 
more rarely, hystero-epileptic seizures, spermatozoa may be found in 
the urine. Such an event is undoubtedly due to muscular spasm. 
and is identical in origin with the emission of semen observed so 
frequently after death, during strangulation, etc. 

In certain spinal diseases semen may be found in the urine, and 
Furbringer relates a most interesting case in which, following frac- 
ture and dislocation of the vertebral column, with partial destruction 
of the middle dorsal cord, spermatorrhcea associated with partial 
erection occurred thirty hours later, and continued until death, 
which took place after three days. 

Most important, however, is the loss of semen noted in cases of 
true spermatorrhcea due to venereal excesses or masturbation, when 
spermatozoa may be found in the urine almost constantly, and the 
diagnosis indeed will often be dependent upon such an observation. 

:.ir as the question of sterility in the male is concerned, reliance 
should not be placed upon an examination of the urine, but the semen 
should be obtained as soon as possible after coitus and examined as 
indicated elsewhere (see p. 532). 

Parasites.. Vegetable Parasites. It has been shown by 
numerous investigations that bacteria are always present both in the 
male and female urethra, and that these may at times gain entrance to 



THE URINE. 505 

the bladder. The weight of evidence, however, is in favor of the view 
that the urine intra vesicam is under normal conditions free from 
micro-organisms, and that auy bacteria which may have found their 
way into the bladder are rapidly killed in healthy individuals. In 
every urine, on the other hand, that has been exposed to the air, 
bacteria arc always preseut. Whenever, then, it is desired to deter- 
mine whether or not the urine of the bladder contains micro- 
organisms, every precaution should be taken to guard against acci- 
dental contamination. To this end the following method should be 
employed : If the patient be a male, he is instructed to hold his 
urine until a fairly large amount has accumulated. The glans is 
then thoroughly washed with soap and water and rubbed off with 
cotton soaked in bichloride solution (1 : 1000). The fossa navicu- 
lars is also thoroiiffhlv cleansed with the same solution. The uriue 
is then voided under as great pressure as possible. The first portion 
(about 100 c.c.) is thrown away, and the second received in a steril- 
ized vessel, when cultures should be made at once, agar or gelatin 
plates beiug inoculated with 1 or 2 c.c. of the urine. In the female 
the vulva is cleansed with soap and water, and the urethral aperture 
disinfected with bichloride solution. After then washing with ster- 
ilized water and drying with sterilized cotton the uriue is evacuated 
through a sterilized metallic or glass catheter and received in a 
sterilized vessel. 

Among the bacteria which may be found iu every urine that has 
been exposed to the air the micrococcus uveas is the only one of 
interest, as ammoniacal fermentation is largely due to its presence. 

When fermentation has commenced it is readily recognized, occur- 
ring in almost pure culture upon the surface of the urine, mostly in 
the form of characteristic chains (Fig. 123). The 
individual coccus is colorless and quite large, so that 
it may be mistaken by the beginner for a blood- S m V*— ^T 
shadow. -*^ s '"*i -T-N 

It is a common error to infer from the occurrence ^\^>o 

of ammoniacal decomposition very soon after mic- -*••-,> 

turition that this process has already begun in the Micrococcus urese. 
bladder. It should be remembered that urine may 
undergo fermentation, particularly in warm weather, shortly after 
having been voided, and especially if the vessel employed is not 
absolutely clean and the urine has been allowed to stand exposed to 
the air. The diagnosis of ammoniacal fermentation in the bladder 



506 CLINICAL DIAGNOSIS. 

should hence only be made when the presence of ammonia can be 
demonstrated in the urine immediately upon being voided. 

The urinary sarcina which is at times met with is smaller than 
that found in the gastric contents, but otherwise presents the same 
appearance. Its presence is of no clinical interest. 

Under pathologic conditions various pathogenic bacteria may be 
eliminated through the urine. Their presence may always be re- 
garded as indicating the existence of some definite alteration of the 
renal parenchyma, but it should be remembered that this need not 
necessarily be in the sense of a nephritis. Pyogenic cocci are espe- 
cially prone to settle in the kidneys and give rise to focal inflam- 
mations, but even without these they frequently pass into the urine. 
In all forms of infectious nephritis an abundant elimination of 
bacteria may probably always be observed, v. Jaksch states that 
in erysipelas the bacteriuria and nephritis disappear together with the 
cessation of the disease. In various suppurative processes taking 
place in the body it has been found that the specific bacteria which 
were frequently observed in the urine disappeared within twenty- 
four to thirty-six hours after the evacuation of the pus. Most in- 
teresting observations have been recently made by Engel in various 
cases of nephritis. Thirty-one cases were examined. In sixteen he 
found the staphylococcus pyogenes albus and aureus, in eight pyo- 
genic streptococci, in four the tubercle bacillus, in one the typhoid 
bacillus, in five the bacillus coli communis, while negative results 
were obtained in only two instances. In the same series, moreover, 
he found a pyogenic coccus in seventeen cases, which was larger 
than the known forms, which could be stained according to Gram's 
method, and which did not liquefy gelatin. Intravenous injection of 
large quantities of the organism produced nephritis in rabbits. 

In pneumonia and pneumococcus infections in general the diplo- 
coccus pneumoniae may be found, and in erysipelas and streptococcus 
infections streptococci. Fairly constant is the presence of the bacillus 
coli communis in cases of pyelonephritis, where it is usually found 
in pure culture, but is at times associated with the staphylococcus 
pyogenes aureus and the proteus Hauser. In some instances the 
latter organism has also been found in pure culture. The typhoid 
bacillus has been repeatedly observed in the urine of typhoid patients. 

Actinomyces kernels may be observed in the urine when the dis- 
ease has attacked the genito-urinary tract or when they have found 
their way into the urine from other organs. 



THE URINE. 507 

Very important is the fact that in tubercular disease affecting the 
urinary organs tubercle bacilli may be found in the urine. The 
search for these, however, is frequently fruitless and always tedious. 
In suspected cases, and particularly in those in which a careful ex- 
amination of the lungs has yielded negative results, an attempt 
should be made to find the organism in the urine. 

Gfrethefs method. To this end the urine is best centrifugated, the 
supernatant fluid removed by means of a pipette, and cover-slips 
prepared. After having been fixed, by being passed through the 
flame of a Bunsen burner, the specimens are stained with a con- 
centrated alcoholic solution of fuchsin under the application of 
heat, washed off in water, and counterstained with a concentrated 
alcoholic solution of methylene-blue at the temperature of the 
room. The excess of the stain is removed by washing with water, 
when the preparations are dried between filter-paper and mounted 
in a drop of cedar oil. The tubercle bacilli will thus be colored 
red, while all other morphologic elements that may be present, 
including the smegma bacilli, are stained blue. The usual methods 
of staining for tubercle bacilli should not be employed when urinary 
deposits are to be examined, as the smegma bacilli, which may 
be found in females as well as in males, are stained in the same 
manner. At the Charite of Berlin the examination is conducted upon 
the slide, when larger amounts of the sediment may, of course, be 
examined at one time. Cover-glasses are not necessary. A drop 
of oil of cedar is placed directly upon the specimen and a ^-immer- 
sion lens employed. 

Very frequeutly it is necessary to prepare a large number of 
cover-glass specimens, but, as stated above, even then the search 
may be without result, notwithstanding the existence of a tuber- 
cular lesion. In such an event it will be best to inject a few drops 
of the sediment into the anterior chamber of the eye of a rabbit, the 
urine being obtained under bacteriologic precautions, and to watch 
for the development of miliary tubercles in the iris. Isolated 
tubercle bacilli have also been found in the urine in cases of acute 
miliary tuberculosis, so that their presence not necessarily indicates 
the existence of tuberculosis of the urinary organs. If, however, 
definite symptoms of renal disease exist at the same time, the diag- 
nosis of renal tuberculosis will probably always be justifiable. 

In this connection it may not be out of place to refer to the 
gonococcus of Neisser, which may now be considered as pathog- 



508 CLINICAL DIAGNOSIS. 

nomonic of gonorrheal infection. The organism (Plate XIV.) 
occurs in the form of small, oval, or round granules, usually 
grouped in twos and fours, so as to resemble a German biscuit 
or the figure 8, enclosed within pus-corpuscles and epithelial cells, 
although they may also occur free in the pus obtained from the 
urethra, in the vaginal discharge, or more rarely free in urinary 
sediments, as in cases of complicating prostatitis, peri-urethritis, 
etc. In making a diagnosis account should only be taken of speci- 
mens which are enclosed in cellular elements, as these alone can be 
regarded as characteristic. They are best stained with Loeffler's 
methylene-blue solution (see p. 109). In cases of urethritis it is 
only necessary to receive a small drop of the discharge upon a 
cover-glass and to spread this out in as thin a layer as possible; 
after drying the preparation is passed through the flame of a Bunsen 
burner three or four times and stained with a drop of the methylene 
solution without the application of heat. The excess of coloring- 

Fig. 124. 



-:"i@ v ^S&-- 






A gonorrhoeal thread. 



m^m^^m^ 



matter is removed by rinsing the specimen in water, when it is 
dried between layers of filter-paper, mounted in a drop of water, 
and examined with an oil-immersion lens, although with a little 
practice reliable results can also be obtained with a lower power. 
In doubtful cases, and especially in women and children, cultures 
should be made, as the organism may at times be confounded with 
the pseudo-gonococci, which are quite frequently present both in the 
diseased aud normal urethra of males and females. The organism 
grows best in a mixture of human blood-serum and nutrient agar 
(1 : 2 or 3 parts). The surface-colonies are pale, grayish, trans- 
lucent, finely granular, with finely notched borders, In bouillon 
and blood-serum mixed it forms a membrane, while the fluid remains 



PLATE XIV 




- m> UP 



L. SCHMIDT. FEC. 



Urethral Discharge from a Case of Gonorrhoea, showing Gonoeoeei Enclosed in 

Pus Corpuscles, and Lying Free in the Discharge. Stained with 

Methylene Blue. (Personal Observation.) 



THE URINE. 509 

clear. Like the pseudo-gonococci, it cannot be stained according to 
Gram's method. 

In conclusion, reference should be made to the occasional occur- 
rence of bactcfiuria of a non-pathogenic form. Such cases are very 
rare, and the diagnosis of idiopathic baoteriuria, as this form may 
be termed, should only be made if every possible source of contami- 
nation of the urine can be definitely excluded. According to Schot- 
telius, this condition is not associated with any pathologic lesion. 

Urines containing bacteria in large numbers are always cloudy, 
and usually present an acid reaction when voided unless a cystitis 
exists at the same time. Attention will be directed to their pres- 
ence by the fact that such specimens cannot be cleared by simple 
filtration. 

Yeast-cells in large numbers are only seen in urines containing 
sugar. Whenever a chemical examination has not been made their 
demonstration will be of importance as suggesting the possible 
existence of diabetes. 

Moulds are usually seen in old diabetic urines after alcoholic 
fermentation has taken place, but may also occur, though far less 
frequently, upon the surface of putrid urines that have contained 
no sugar. 

Animal Parasites. The organism which Hassal saw in a urine 
that had been "freely exposed to the air" and was alkaline, and 
which he termed Bodo urinarius, was in all probability an infuso- 
rial monad and of no pathologic significance. Salisbury was the 
first to point out that the " trichomonas vaginalis" of Donne may 
at times occur in the bladder, but gave no detailed account of his 
cases. Kunstler, Marchand, Miura, and Dock then reported cases 
in which flagellate protozoa were found, and modern research leaves 
no doubt that the organisms described by these observers are iden- 
tical with the trichomonas of Donne. In Miura's case the habitat 
of the parasite was the urethra, and an examination of the patient's 
wife revealed the presence of similar organisms in the vagina. 
Kiiustler's case was one of pyelitis following cystotomy. Mar- 
chand's patient had a fistula in the perineum following suppura- 
tion in the pelvis of unknown origin; cystitis did not exist. Dock's 
case was associated with hsematuria. Within the last year the 
writer likewise found a trichomonas in the urine of a female patient 
occurring in the practice of Dr. W. M. Lewis, of Baltimore. The 
case was one of cholelithiasis. The urine contained blood in fairly 



510 CLIXICAL DIAGNOSIS. 

large amount. Evidence of cystitis and nephritis did not exist. 
The number of the parasites was small. 

Balz observed numerous amoebae in the turbid urine of a eirl the 
subject of phthisis, which he described as being of larger size than 
the amoeba coli. Ciliated infusoria have also been found in the 
urine in isolated cases. 

The ova of distoma haematobium and the filaria sanguinis hominis 
are at times found in the urine, their elimination being; usnally 
accompanied by haeinaturia and chyluria. Echinococcus booklets 
and fragments of cysts may also be found, and in rare instances 
ascarides find their way into the urinary passages when a fistulous 
opening exists between the rectum and the bladder. Bothrioeeph- 
alus linguloides, Leuckart, was found in the urine in one case occur- 
ring in Eastern Asia. Eustrongylus gigas is likewise found very 
rarely. Moscato records one case in which chyluria existed at the 
same time. 

Tumor-particles. Tumor-particles are so rarely seen in the 
urine that a detailed account of their occurrence may be omitted, 
particularly so as it is seldom possible to base the diagnosis of tumor 
upon the presence of fragments in the urine, the clinical history and 
the physical signs being usually sufficient to reach a satisfactory diag- 
nosis. 

Foreign Bodies. Among foreign bodies which may be found 
in the urine may be mentioned particles of fat, fibres of silk. 
linen, aud wool, etc.; in short, material the presence of which is 
owing to the use of unclean vessels for the reception of the urine. 
Fecal matter may be passed per urethram ; such an occurrence, of 
course, always indicates the existence of an abnormal communi- 
cation between the bowel and the urinary passages, especially the 
bladder. Hair derived from a dermoid cyst may similarly be 
found. In hysteria foreign bodies of almost any kind may be 
shown the physician as having been passed in the urine, such as 
hair, teeth, fish-bones, wood, etc., and even snakes and frogs. The 
author had occasion to examine " gravel" ;i passed " from time to 
time by an hysterical patient in large amounts, " every attack being 
accompanied by the most agonizing pains shooting down into the 
lower abdomen;'' the gravel upon examination proved to be mortar, 
obtained from the cellar of the patient's house. 



CHAPTEE VIII. 

TRANSUDATES AND EXUDATES. 

DEFINITION. 

In health the so-called serous cavities of the body contain but 
very little fluid, and quantities sufficient for analytical purposes can 
normally only be obtained from the pericardial sac. In pathologic 
conditions, on the other hand, large accumulations of fluid may be 
observed not only in the serous cavities, but also in the areolar con- 
nective tissue, beneath the skin, and beneath the muscles. When 
due to circulatory disturbances, a hydremic condition of the blood, 
or an insufficient elimination of water through the kidneys, such 
accumulations of fluid are spoken of as transudates, while the term 
exudates is applied to similar accumulations of inflammatory origin. 

Clinically, it is frequently difficult to distinguish between trans- 
udates and exudates, and large ovarian, pancreatic, and hydatid cysts, 
as well as cystic kidneys, may at times be mistaken for ascites. In 
such cases a careful chemical and microscopic examination of the 
fluid in question may be of decided value.. Very frequently, more- 
over, it is possible only in this manner to determine the true nature 
of the disease, and the importance of freely using the trocar and the 
aspirating-needle in diagnosis cannot be too strongly advocated. 

TRANSUDATES. 

General Characteristics. 

Transudates are usually serous in character, when they present a 
light-straw color ; at times, however, owing to an admixture of 
blood, they have a reddish tinge, and are then spoken of as san- 
guineous ; in rare instances they are chylous. 

The Specific Gravity. 

The specific gravity varies somewhat according to the origin of 
the fluid, but is usually lower than that of serous exudates occurring 
in the same cavities, one of the most important points of difference 
between the two kinds of fluid. Thus, in acute pleurisy the specific 
gravity of the exudate is usually higher than 1.020, and in chronic 



512 



CLIXICAL DIAGX'. i. 



pleurisy, if an accumulation of pus exists at the same time, higher 
than 1.018, aud even reaching 1.030. In transudates into the 
pleural cavity, on the other hanc^ referable to circulatory disturb- 
ances, for example, as in cases of hepatic cirrhosis or cardiac insuffi- 
ciency, the figures obtained are usually lower than 1.015. Transu- 
dates of peritoneal origin similarly present a specific gravity varying 
between 1.005 and 1.015, while that of exudates frequently reaches 
1.030. 

As the chemical composition, in so far as the mineral constituents 
and extractives are concerned, is practically the same in both classes 
of fluid, the difference in the specific gravity appears to be essentially 
due to the amount of albnmin present, viz.. serum-albumin and 
serum-globulin. It may be demonstrated, as a matter of fact, that 
exudates contain far more albnmin than transudates, the amount 
varying between 4 and 6 per cent, in the former as compared with 
1 and 2.5 per cent, in the latter. The largest amounts of albumin 
in transudates are found in those of pleural origin, while in oedema 
not more than 1 per cent, is usually present. 

In the table be! ow, taken from Reuss/ the relation between the 
percentage-amount of albumin and the corresponding specific gravity 
is shown. Reuss suggested the following formula for the purpose 
of determining from the specific gravity the amount of albumin in 
transudates and exudates : 



E = _ S — 1000) — - ; 

a 



in which "E ,J indicates the percentage-amount of albumin and 
" S " the specific gravity, taken by means of an accurate urinometer. 



Specific gravity. 

1.008 . 

1.009 . 

1.010 . 

1.011 . 

1.012 . 

1.013 . 

1.014 . 

1.015 . 

1.016 . 

loh 

1.015 . 



- 
0.6 
1.0 

1.3 
1.7 

2.1 

1 ' 

2 3 
3.2 

3.6 
4.0 



1.019 . 

1.020 . 

1.021 . 

: .:_ 
: m 

1.024 . 
1.02-5 . 

: . :.; 
i :_- 

1.028 



5.1 
5.5 

\ a 
i - 

- .: 

7.3 



The following table shows the percentage-amount of albumin 
obtained by Runeberg in ascitic fluid under various pathologic con- 
ditions : 



TRANSUDATES AND EXUDATES. 



513 



Hydremia (Blight's disease, tuberculosis, 
etc., with amyloid degeneration) . 0.21 

Portal stasis (referable to hepatic cirrhosis 
or stenosis") 0.97 

General venous stasis (referable to organic 

heart disease) . . . . .1.67 

Carcinoma of the peritoneum (compli- 
cated with carcinoma of the stomach). 3.51 

Chronic peritonitis (one case complicated 

with heart disease) . . . .3.71 



Average, Maximum. Minimum, 



0.41 



2.68 



2.30 



5.42 



4.25 



0.03 



0.37 



0.84 



2.70 



3.36 



The fact, moreover, that transudates do not coagulate spontaneously 
in the absence of blood may further serve to distinguish these from 
exudates, in which a coagulum is frequently observed after having 
stood for twenty-four hours. But not much reliance should be 
placed upon this point of difference, as exudates likewise do not 
always coagulate, and clotting of transudates in the presence of 
blood may already take place within the body. 



The Chemistry of Transudates. 

An idea of the chemical composition of the various forms of transu- 
dates may be formed from the following tables, taken from Hoppe- 
Seyler and Haramarsten, the figures corresponding to 1000 parts by 
weight of fluid, and the specimens being taken from one individual : 



Water 
Solids 
Albumin . 
Ethereal extract "] 
Alcoholic extract i 
Aqueous extract \- 
Inorganic salts 
Errors of analysis J 



Pleura. 

957.59 
42.41 

27.82 



14.59 



Peritoneum. 

967.68 
32.32 
16.11 

5.27 



10.94 



Analysts of Hydeocele Fluid 



Water . 
Solids . 
Fibrin (formed) 
Globulins 
Serum-albumin 
Ethereal extract 
Soluble salts . 
Insoluble salts 
Sodium chloride 
Sodium oxide 



CEdema of 
the feet. 

982.17 
17.83 
3.64 
0.50 
3.71 
1.10 
9.00 
0.12 



938.85 

61.15 

0.59 

13.52 

35.94 

4.02 

8.60 

0.66 

6.19 

1.09 



33 



514 CLINICAL DIAGNOSIS. 

Sugar aDd uric acid in small amounts are also, as a rule, found in 
transudates, and in one ease of hepatic cirrhosis Moscatelli succeeded 
in demonstrating the presence of allantoin. 



Microscopic Examination. 

Upon microscopic examination only a few isolated leucocytes and 
endothelial cells derived from the serous surfaces and undergoing 
fatty degeneration are seen. In cases in which the transudates have 
been confined for a long time in one of the serous cavities plates of 
cholesterin are frequently found. These appear to be especially 
abundant in hydrocele fluid. 

EXUDATES. 

Exudates may be serous, sero- fibrinous, sero-purulent, purulent, 
putrid, hemorrhagic, chylous, or chyloid, terms which do not require 
further definition. 

The purulent, sero-purulent, and putrid forms are manifestly of 
inflammatory origin, while it may at times be difficult to decide the 
true nature of serous, sero-fibrinous, and sero-sanguineous fluids. In 
such, cases the points of difference already described between transu- 
dates and exudates should be borne in mind, and will, when taken 
in conjunction with the physical signs and the clinical history, gen- 
erally lead to a correct diagnosis of the origin of the fluid. 

Serous Exudates. 

Serous exudates are clear, of a light- straw color, and present a 
specific gravity usually exceeding 1.008. After standing, a white, 
fibrinous coagulum is generally formed. Upon microscopic exami- 
nation some red corpuscles, which are probably referable to the 
puncture, polynuclear leucocytes, and endothelial cells undergoing 
fattv defeneration are found. Such exudates, as indicated, differ 
from the corresponding transudates in presenting a higher specific 
gravity, and in the fact that clotting is observed in transudates only 
in the presence of blood. Exudates, however, do not invariably 
coagulate, and too much importance should hence not be attached to 
this point. 



TBANSUDATES AND EXUDA TES. 515 

Hemorrhagic Exudates. 

Hemorrhagic exudates are essentially serofibrinous in character, 
the exact color depending upon the amount of blood-pigmeut present. 
Microscopic examination reveals the presence of a large number of 
red corpuscles, poly nuclear leucocytes, and endothelial cells. Choles- 
tcrin-crvstals may also at times be seen, though rarely in very large 
numbers. When numerous, attention is readily drawn to them, dur- 
ing the macroscopic examination of the fluid, by the peculiar glisten- 
ing appearance of its surface. 

Tuberculosis. As hemorrhagic exudates are most commonly 
observed in cases of tuberculosis and of carcinoma of the luugs and 
pleura, the specimen should be carefully examined for tubercle bacilli 
and cancer-cells. In every case it will be best to subject portions 
of the fluid to centrifugation and to examine the sediment thus 
obtained. Usually tubercle bacilli are not found, even when tuber- 
culosis of the pleura exists. If in such cases culture-experiments 
likewise prove negative and cancer-cells are not found, the diag- 
nosis of probable tuberculosis will nevertheless be warrantable. 

Cancer. The diagnosis of cancer should be based upon the 
demonstration of cancer-cells in the fluid. The physician, however, 
is warned not to mistake endothelial cells for caucer-cells. The 
diagnosis should hence only be made when large epithelial cells of 
variable form, measuring at times 120 [x in diameter, are found in 
large numbers, especially when arranged in groups, unless, indeed, 
cancerous nodules presenting the characteristic alveolar structure are 
at once found. Quincke has drawn attention to the occurrence of 
large numbers of fat-droplets, which may attain a diameter of from 
40 fj. to 50 p. in the fluid in cases of neoplasm. At times these fat- 
droplets are so small and numerous as to give a chylous appearance 
to the exudate. At other times a similar appearance is due to the 
presence of minute albuminous granules, which may be readily dis- 
tinguished from the former by their insolubility in ether. The 
occurrence of numerous fatty-acid crystals arranged in groups should 
likewise be regarded as favoring the diagnosis of carcinoma. It is 
also claimed by Quincke that carcinoma probably exists if a marked 
glycogen reaction can be obtained in the endothelial cells. This test 
has already been described in the chapter on Blood (see p. 46). 

Rieder has lately called attention to the occurrence of cells under- 
going division, their nuclei presenting essentially typical karyokinetic 



516 CLINICAL DIAGNOSIS. 

figures, which he regards as pathognomonic of carcinoma. Cover- 
slip preparations are prepared from the sediment, dried in the air, 
fixed by immersion for an hour in a mixture of equal parts of abso- 
lute alcohol and ether, and stained with a dilute solution of hsema- 
toxylin. 

Putrid Exudates. 

Putrid exudates are observed following the perforation of a gan- 
grenous focus or of a gastric or intestinal ulcer into one of the body- 
cavities. At other times they are encountered in cases of neoplasm 
and at times even without any apparent cause. The material 
obtained in such cases presents a brown or brownish-green color, 
and emits an odor which in itself indicates the character of the exu- 
date. Microscopically cholesterin, hsematoidin, and fatty-acid crys- 
tals, as well as degenerating leucocytes, are found. In cases in 
which aspiration of a higher intercostal space reveals the presence 
of serous fluid, while putrid material is obtained at a lower point, 
the existence of a subphrenic abscess should be suspected. In such 
cases a pure culture of the bacillus coli communis has been obtained. 
The reaction of putrid exudates is usually alkaline, but an acid 
reaction may be obtained in cases of perforation of a gastric ulcer; 
the sarcina ventriculi and saccharomyces may then be found. 

Pus. 

General Characteristics of Pus. If pus, which usually 
presents a color varying from yellowish-gray to greenish-yellow, 
be allowed to stand for some time, a liquid gradually appears at 
the top, increasing in amount, until it is finally possible to dis- 
tinguish two distinct layers, the one above — the pus-serum, the other 
at the bottom — the pus-corpuscles. Upon the number of the latter 
the consistence as well as the specific gravity of the pus is depend- 
ent. This may vary between 1.020 and 1.040, with an average 
of 1.031 to 1.033. Fresh pus has always an alkaline reaction, 
which may become neutral or slightly acid upon standing, owing 
to the development of free fatty acids, glycerin-phosphoric acid, 
and lactic acid. The color of pus-serum may be a light straw, a 
greenish, or a brownish-yellow. 

The Chemistry of Pus. The chemical composition of pus- 
serum and pus-corpuscles may be seen from the following tables: 



TBANSUDATES AND EXUDATES. 



517 



Analysis of Pus-serum. 



Water 
Solids 
Albumins . 
Lecithin . 
Fat . 

Cholesterin 
Alcoholic extract 
Aqueous extract 
Inorganic salts . 



Analysis of Pus-corpuscles. 



1. 


II. 


. 913.7 


905.65 


. 86.3 


94.35 


. 63.23 


77.21 


. 1.50 


0.56 


. 0.26 


0.29 


. 0.53 


0.87 


1.52 


0.73 


. 11.53 


6.92 


. 7.73 


7.77 


USCLES. 




I. 


ir. 


. 137.62 




. 342.57 


f 673.69 
1685.85 


. 205.66 




143.83 


f 75.61 

t 75.00 


. 74.0 


72.83 


. 51.99) 
. 44.33 J 


101.84 



Albumins . 
Xuclein . 

Insoluble matter 
Lecithin \ 
Fat / 

Cholesterin 
Cerebrin . 
Extractives 



Peptone is usually present, being derived from the pus-corpuscles. 
Leucin and tyrosin are likewise frequently met with in the pus of 
old abscesses, and fatty acids, urea, sugar, glycogen, biliary pig- 
ments, and acids (in catarrhal jaundice), acetone, uric acid, several 
xanthin bases, cholesterin, etc., have occasionally been observed. 

Microscopic Examination of Pus. Leucocytes. If a drop 
of pus be examined with the microscope, it will be seen to contain 
innumerable leucocytes, the diameter of which varies from 8 p. to 
10 /z, and which in fresh pus exhibit the characteristic amoeboid move- 
ments. It is curious to note that the so-called lymphycotes do not 
occur in pus, and even in the rare cases in which a predominance 
of this variety is met with in the blood, as in cases of lymphatic 
leukaemia, it will be observed that only the larger forms occur in 
the pus of abscesses which may have formed. While the leucocytes 
of fresh pus usually present a normal appearance, specimens may be 
observed in which amoeboid movements can no longer be observed, 
even upon the application of heat, and in which rounded vacuoles, 
filled with a clear liquid, and fatty granulations in moderate numbers 
may be seen. A predominance of such dead leucocytes usually in- 



518 CLINICAL DIAGNOSIS. 

dicates that the pus is old or has been formed in greatly debilitated 
subjects. 

Owing to a resorption of water in accumulations of pus of long 
standing such material finally assumes a caseous aspect, and the 
leucocytes will be seen to have greatly diminished in size, and to 
have assumed an angular, shrunken appearance; it is then hardly 
possible to demonstrate the presence of a nucleus even after the addi- 
tion of acetic acid. 

It is noteworthy that in cases of hepatic abscess referable to the 
amoeba coli it is seldom possible to demonstrate any normal leuco- 
cytes, the pus upon microscopic examination consisting essentially 
of granular and fatty detritus, while in liver-abscesses due to other 
causes the leucocytes usually present a fairly normal appearance. 

Giant corpuscles. So-called giant pus-corpuscles, measuring at 
times from 30 p. to 40 //. in diameter, have been observed in abscesses 
of the gum, hypopyon, and in the contents of suppurating ovarian 
cysts, but do not appear to have any special significance. Upon 
careful examination these bodies will be seen to contain one oval 
nucleus, usually located excentrically within the cell, and from one 
to thirty or even forty pus-corpuscles. 

Detritus. Fatty and albuminous detritus in variable amount may 
be observed in every specimen of pus, increasing with the length of 
time that the latter has been confined within the body. The same 
holds good for the presence of free nuclei, which were formerly 
regarded as young pus-corpuscles, but which have now been defi- 
nitely recognized as originating during the disintegration of the 
corpuscles. 

Red corpuscles. Red blood-corpuscles in variable numbers are 
usually seen in every specimen, their appearance depending upon 
the length of time that they have been confined. Pus-corpuscles 
may at times be seen to contain a red corpuscle. 

In doubtful cases it is always well to search carefully for the 
presence of tissue-elements, as it is at times possible only in this 
manner to recognize the true character of the morbid process. As 
the data of importance have already been detailed in other sections 
of this book (viz., Sputum and Urine), it will be unnecessary to 
recapitulate at this place. 

Pathogenic vegetable parasites. Among the pathogenic organisms 
encountered which are of especial interest from a clinical standpoint 
there may be mentioned the true pus-organisms, notably the staphy- 



TRANSUDATES AND EXUDATES. •,!<) 

lococcus pyogenes aureus and the streptococcus pyogenes ; further- 
more, the tubercle bacillus, the bacillus of syphilis, the actinomyces 
hominis, the bacillus of glanders, the bacillus of anthrax, leprosy, 
tetanus, influenza, and Frankel's pneumococcus, etc. The majority 
of these have already been described, and the reader is referred for 
more detailed information to special works on bacteriology. In this 
connection it will be sufficient to state that, so far as pleural exu- 
dates are concerned, an absence of micro-orgauisms is usually indica- 
tive of tuberculosis, while the preseuce of FriiukePs pneumococcus 
in exudates forming in the course of a pneumonia appears to be a 
favorable omen, as far as the origin of the pleurisy is concerned. 

Protozoa, with the exception of the amoeba coli, have only rarely 
been found. Kunstler and Pitres observed numerous large spores 
with from ten to twenty crescentic corpuscles in the pus taken from 
the pleural cavity of a man, which closely resembled the coccidia of 
mice. Litten observed cercomonads in the fluid withdrawn from 
a pleural cavity. Trichomonads have been found in a case of 
empyema. 

Most importaut in this connection is the demonstration of the 
presence of the amoeba coli in the pus, and in cases of liver-abscess 
an examination with this view should never be neglected, as the 
prognosis to a large extent will depend upon the results obtained. 
As far as the occurrence of amoebae in pus is concerned, the observa- 
tion of Flexner, who demonstrated their presence in an abscess of 
the lower jaw, shows that they should not be looked for in the pus 
of abscesses of the liver only. 

Vermes. Of these, the filaria and hydatids are very rarely 
observed in this country. Bothriocephalus leguloides has been 
found in the pleural cavity of a Chinese patient. 

Crystals. As has been stated, crystals of cholesterin are fre- 
quently found in old pus and in exudates of long standing, but are 
rarely seen in recent exudates. They may be recognized by their 
characteristic form and their chemical reactions, as described in the 
chapter on Feces (p. 195). Triple phosphates, fatty-acid crystals, 
and haeniatoidin are likewise frequently seen, the presence of the 
latter, of course, indicating a previous admixture of blood. 

Chylous and Chyloid Exudates. 

Chylous and chyloid exudates have been repeatedly observed. 
They are most frequently met with in the abdominal cavity (104 



520 CLINICAL DIAGNOSIS. 

times out of the total number of 155, which have thus far been 
reported), less commonly in the pleural cavity (forty-nine times), 
and only rarely in the pericardial sac (twice only). Quincke 
believed that the two forms can be etiologically distinguished from 
one another by means of a microscopic examination, as the cloudy 
appearance in the chyloid form is usually referable to the presence 
of endothelial or epithelioid cells undergoing fatty degeneration. 
Later observations, however, have shown that the differentiation of 
the two forms cannot be made upon this basis, as the same anatom- 
ical changes, such as carcinoma, may at times give rise to the forma- 
tion of a chylous exudate, at others to that of the chyloid form, and 
both, moreover, may coexist. Senator claimed that the presence of 
more than mere traces of sugar is strongly suggestive of the chylous 
nature of the exudate. Possibly this observation may be of some 
value, but it must not be forgotten that sugar is quite commonly 
met with in all forms of transudates and exudates. The presence 
of more than 0.2 per cent, can only be of value. 

Chylous exudates in their general appearance resemble milk, while 
the chyloid fluid is more suggestive of pus. The turbidity in both 
cases is usually referable to the presence of innumerable fat globules, 
which are especially abundant in the chylous form. In chyloid exu- 
dates the origin of the fat from cellular elements is often apparent at 
once, but, as has been said, it is impossible to draw definite etiologic 
conclusions from that difference. Some chyloid exudates contain no 
fat at all, and Lion has shown that the milky appearance in such 
cases is owing to the presence of a curious albuminous substance, 
belonging to the class of nucleo-albumins. 



CHAPTEK IX. 

THE EXAMINATION OF CYSTIC CONTENTS. 
CYSTS OF THE OVARIES AND THEIR APPENDAGES. 

The material obtained from cysts of the ovaries or their appen- 
dages varies greatly in character. On the one hand, it may be fluid, 
clear, of low specific gravity, and containing but little albumiD, 
while, on the other, it may be dense, viscous, of colloid appearance, 
and of specific gravity varying between 1.018 and 1.024, owing 
to the presence of a large amount of albumin, viz., serum-albumin, 
serum-globulin, and, most important of all, metalbumin or paral- 
bumin. The latter is almost constantly met with in ovarian cysts, 
and its presence is quite characteristic of fluids derived from this 
source. 

lest for metalbumin. The fluid is mixed with three times its 
volume of alcohol and set aside for twenty-four hours, when it is 
filtered and the precipitate suspended in water. This is again 
filtered and the filtrate tested in the following manner : 1. A few 
c.c. are boiled, when in the presence of metalbumin the liquid will 
become cloudy, without, however, the formation of a precipitate. 
2. With acetic acid no precipitate is obtained. 3. Upon the appli- 
cation of the acetic acid and potassium ferrocyanide test the liquid 
becomes thick and assumes a yellowish color. 4. When boiled with 
Millon's reagent a few c.c. of the filtrate will yield a bluish-red 
color, while the addition of concentrated sulphuric acid, without 
boiling, gives rise to a violet color. 

The color of cystic fluids may vary from a light straw to a red- 
dish-brown, or even chocolate; the latter color may be observed 
when hemorrhage has taken place into the cyst. 

Of morphologic elements, ovarian cysts contain red blood-cor- 
puscles, leucocytes, and at times fatty granules in large numbers, 
crystals of cholesterin, hsematoidin, and fatty acids. Most impor- 
tant, however, from a diagnostic standpoint is the presence of cylin- 
drical or prismatic ciliated epithelial cells, derived from the internal 
lining of the cyst, in the presence of which the diagnosis may be 



522 



CLINICAL DIAGNOSIS. 



definitely made. (Fig. 125.) At times such cells cannot be demon- 
strated, owing to their having undergone fatty degeneration ; more- 
over, if the epithelium, lining the cyst, be squamous in character, it 
may be difficult, if not impossible, to arrive at a satisfactory con- 
clusion from an examination of the morphologic elements alone. 
Colloid concretions, which may vary in size from several micromilli- 
meters to 0.1 mm., are occasionally observed, more particularly in 
cases of colloid cysts. They may be recognized by their irregular 
form, their homogeneous appearance, their slightly yellowish color, 
and delicate outlines. 



Fig. 125. 




Contents of an ovarian cyst. (Eye-piece III , obj. 8 a, Reichert.) (v. Jaksch.) 
a. Squamous epithelial cells, b. Ciliated epithelial cells, c. Columnar epithelial cells, d. 
Various forms of epithelial cells, e. Fatty squamous epithelial cells. /. Colloid bodies, g. 
Cholesterin crystals. 

In dermoid cysts, epidermal cells and occasionally hair are 
observed, in which case the diagnosis is no longer doubtful. 

The differential diagnosis of ovarian, parovarian, and fibro-cystic 
(uterine) cysts cannot always be made by the characters of the fluid 
withdrawn by puncture, but at times it is possible. The most 
important points of difference are here given : 1. The fluid in ovarian 
cystomata is usually more or less viscid, and often contains non- 
nucleated granular corpuscles about the size of leucocytes, the gran- 
ules not dissolving in acetic acid, nor disappearing when treated with 
ether. In all probability they are free nuclei and are often called 
Drysdale's corpuscles in our country. 2. In parovarian cysts the 



THE EXAMINATION OF CYSTIC CONTENTS. 523 

fluid is thin, watery, of low specific gravity (under 1.010), and con- 
tains very few morphologic elements. Cylindrical epithelium is 
very rarely found in the fluid withdrawn by aspiration from either 
ovarian or parovarian cysts during life. 3. The fluid from fibro- 
cystic tumors of the uterus is thin, watery, and spontaneously coag- 
ulable, while that from ovarian and parovarian cysts never coagulates 
spontaneously, unless blood be present. Fibro-cystic tumors of the 
uterus have no epithelial lining. 

HYDATID CYSTS. 

Hydatid cysts are scarcely ever seen in this country, and may 
practically be excluded in a differential diagnosis. The fluid in 
question is clear, alkaline, of a specific gravity varying between 
1.006 and 1.010, and contains no albumin. Succinic acid is usually 
present, and may be demonstrated by acidifying a small amount of 
the fluid with hydrochloric acid and evaporating to dryness. The 
residue is extracted with ether and the ether evaporated, when the 
aqueous solution of the second residue in the presence of succinic 
acid will yield a rust-colored gelatinous precipitate when treated 
with a few drops of a solution of the sesquichloride of iron. Sodium 
chloride is always present in notable amounts and may be recognized 
by evaporating a drop of the liquid upon a slide, when the charac- 
teristic crystals of salt will be found. Most important, of course, 
is the microscopic examination, which may reveal the presence of 
hooklets and shreds of membrane, and at times of scolices (see 
Sputum). 

HYDRONEPHROSIS. 

The diagnosis of hydronephrosis can usually be made without 
difficulty if a sufficient amount of fluid can be obtained, as the pres- 
ence of urea and uric acid in notable quantities, as well as of renal 
epithelial cells, which latter especially should be sought for, is quite 
characteristic. Small amounts of uric acid may also be present in 
ovarian cysts. 

PANCREATIC CYSTS. 

These cysts may be recognized by the fact that the fluid possesses 
the power of digesting albumin in alkaline solutions. A small 
amount of the liquid is added to milk, when after precipitation 



524 CLINICAL DIAGNOSIS. 

of the casein the biuret test is applied, a positive reaction indi- 
cating the presence of trypsin. Unfortunately, however, this test 
does not always yield positive results, even if the fluid in ques- 
tion be derived from a pancreatic cyst, as the trypsin is apparently 
destroyed in the course of time. The larger the size of the cyst, 
the less likely will it be possible to obtain the reaction described. 
A positive result is hence only of value, while a negative result 
does not exclude the existence of the disease. 



CHAPTER X. 

THE EXAMINATION OF THE CEREBROSPINAL FLUID. 

According to our present knowledge, the cerebro-spinal fluid is 
secreted by the choroid plexuses into the lateral ventricles. Passing 
through the foramina of Monroe, the third ventricle, and the aque- 
duct of Sylvius, on the one hand, it reaches the fourth ventricle and 
enters the cistern-like subarachnoid spaces at the base of the brain 
through the foratneu of Magendie and the lateral clefts of the fourth 
ventricle. On the other hand, a certain portion of the fluid reaches 
the same destination directly through the cleft in the descending 
horn of each lateral ventricle. The larger portion of the fluid then 
passes upward through the subarachnoid spaces along the convexity 
of the brain to the Pacchionian granulations, while the smaller por- 
tion enters the vertebral canal through the subarachnoid spaces of 
the spinal arachnoid membrane. 

Within recent years puncture of the vertebral canal has been 
resorted to repeatedly, not only for therapeutic purposes, but also 
for diagnostic purposes, after Quincke had drawn attention to the 
fact that cerebro-spinal fluid can thus be obtained with comparative 
ease. The practical value of this new method of diagnosis is now 
beyond question, and it is to be hoped that ere long physicians will 
resort to spinal puncture in obscure cases of cerebro-spinal disease 
with as little hesitancy as puncture of the thoracic and abdominal 
cavities is now practised. 

The operative method to be employed is the following: With the 
patient placed upon his left side — some observers prefer the sitting- 
posture — and the body bent well forward, a long aspi rating-needle 
is introduced upon a level with the lower third of the third or fourth 
lumbar spinous process and a little to the side of the median line, 
the needle being directed slightly upward and inward. The depth 
to which it is necessary to puncture will, of course, vary with the 
age of the patient. In a child two years of age the vertebral canal 
may be reached at a depth of two centimetres, while in the adult 
it is necessary to insert the needle for a distance of from 4 to 8 cm. 



526 CLINICAL DIAGNOSIS: 

As soon as the subarachnoid space is reached the ce rebro-spinal fluid 
will flow from the needle. Aspiration should always be avoided. 

Some writers have advised that the operation should be performed 
under narcosis, and without doubt this may be uecessary at times, 
particularly when contracture of the dorsal muscles exists. In the 
majority of cases, however, it is probably not necessary. 

Amount. As far as the writer has been able to ascertain, no 
observations have thus far been made regarding the amount of fluid 
which may be obtained by puncture in normal individuals. In all 
probability, however, this is small. Under pathologic conditions 
the amount may vary from a few drops to 100 c.c, and even more. 
In general terms it may be stated that the amount is directly pro- 
portionate to the degree of intra-cranial pressure. Exceptions, how- 
ever, are frequent. Small amounts of cerebro- spinal fluid or none 
at all may thus be obtained, when owing to the formation of a thick 
exudate or the existence of a cerebral tumor the communication 
between the basilar subarachnoid spaces of the brain and those of 
the spinal cord has been interrupted. Whenever, then, symptoms 
of intra-cranial pressure exist, while no fluid or minimal amounts 
only can be obtained by puncture, the conclusion will usually be 
justifiable that we are dealing with a purulent meningitis or with 
a tumor of the brain, and more especially of the cerebellum. It 
should be remembered, however, that the same result may be reached 
in cases of obliteration of the aqueduct of Sylvius or when sclerotic 
processes involve the foramen of Magendie, which is occasionally 
observed in certain forms of hydrocephalus. Adhesions of the pia 
mater with the arachnoid and the dura mater may, by interfering 
with the flow of cerebro-spinal fluid, also lead to the formation of 
hydrocephalus, but in these cases a tumor can usually be excluded, 
as the changes in question always develop as sequelae to a meningitis. 
A serous or tubercular meningitis, as w T ell as acute hydrocephalus 
and tetanus, can, however, always be excluded when only minimal 
amounts of fluid are obtained by puncture. The largest amounts, 
on the other hand, are seen in cases of serous meningitis, tubercular 
meniugitis, and cerebral tumors, which do not interfere with the 
circulation of the cerebro-spinal fluid. 

Appearance. Normal cerebro-spinal fluid, as well as that 
obtained in cases of serous meningitis, tubercular meningitis, 
hydrocephalus, and tumors of the brain, is perfectly clear, and 
as a rule colorless, unless indeed a small bloodvessel has been 



THE EXAMINATION OF THE CEREBROSPINAL FLUID. 527 

punctured, when the fluid may present a slightly reddish tinge. 
More or less pronounced yellow shades are, however, also at times 
observed. Important from the standpoint of diagnosis is the fact 
that in cases of hemorrhage into the ventricles pure blood is obtained, 
while such a result is, of course, a mechauical impossibility in cases 
of epidural hsematoma. In subdural hsernatoma, on the other hand, 
blood may also find its way into the subarachnoid space, but the 
amount is always small, and cannot be compared to that seen in 
cases of ventricular hemorrhage. Whenever, then, as in traumatic 
cases with severe cerebral symptoms, the surgeon is confronted with 
the question whether or not to trephine, puncture of the subarach- 
noid space may furnish much valuable information. If in such 
cases no blood at all is obtained, it may be inferred that an epidural 
hsematoma or a subdural hematoma of slight extent only exists; an 
operation might then be performed. If, however, pure blood be 
found, it would be justifiable to assume the existence of extensive 
injury to the brain-substance proper, or in cases in which the history 
of the case is obscure an intra-cerebral hemorrhage with rupture into 
the ventricles. In such cases the idea of an operation would, of 
course, only be entertained under exceptional conditions. If, fur- 
ther, the fluid is only tinged with blood a subdural hematoma prob- 
ably exists, aud an operation could be advised. Accidental hem- 
orrhage, viz., hemorrhage referable to the puncture itself, can be 
readily recognized, as the first few drops only are then tinged with 
blood, or the blood appears only after the flow has been definitely 
established; the amount, moreover, is insignificant. 

Cloudy fluid is obtained in all cases of purulent meningitis unless 
this be limited to a very small area. This is, of course, most impor- 
tant from a diagnostic standpoint. Cases of abscess of the brain 
or sinus thrombosis occur again and again in which the question 
as to the advisability of operative interference is largely depen- 
dent upon the presence or absence of a complicating purulent menin- 
gitis. In certain instances a satisfactory conclusion may, of course, 
be reached without puncture; but in many others this is impossible, 
and Lichtheim's dictum that an operation should never be under- 
taken in such cases unless the integrity of the meninges has been 
established by spinal puncture should be borne in mind. 

The degree of cloudiness naturally varies in different cases, and 
while in some instances the character of the fluid is sero-purulent, 
pure, creamy pus may be found in others. Generally speaking, a 



528 



CLINICAL DIAGNOSIS. 



cloudy fluid indicates the existence of an acute inflammatory process 
or an acute exacerbation of a chronic process. 

Important, furthermore, is the fact that the fluid in non-inflam- 
matory diseases of the brain, such as tumor or abscess, rarely under- 
goes coagulation, while this is the rule in all inflammatory diseases. 
In tubercular meningitis the coagula are very delicate, and may be 
well compared to spider-webs, extending throughout the fluid, while 
in purulent meningitis the coagula are much firmer. 

Specific Gravity. The specific gravity of cerebro-spinal fluid 
normally varies between 1.005 and 1.007, corresponding to the 
presence of from 10 to 15 p. m. of solids. Under pathologic con- 
ditions variations from 1.003 to 1.012 may be observed, the specific 
gravity, generally speaking, being higher in the inflammatory than 
in the non-inflammatory diseases of the brain. From a diagnostic 
standpoint, however, the determination of the specific gravity is of 
no special interest, as numerous exceptions occur to the above rule. 

The reaction is always alkaline. 

Chemical Composition. An idea of the chemical composition 
of the cerebro-spinal fluid may be formed from the following anal- 
ysis, taken from Gautier : 



987.00 
1.10 
0.09 
0.21 

2.75 



6.14 
0.10 
0.20 



Water . 

Albumin 

Fat 

Cholesterin . 

Alcoholic and aqueous extract, minus salts 

Sodium lactate 

Chlorides 

Earthy phosphates 

Sulphates 

Ammonia 

In addition urea is at times found, as also a substance which 
reduces Fehling's solution and gives rise to a brown color when 
boiled with caustic potash, but which neither undergoes fermenta- 
tion nor forms an osazon when treated with phenylhydrazin. The 
substance in question is generally regarded as pyrocatechin. Its 
amount varies between 0.002 and 0.116 per cent. According to C. 
Bernard, moreover, glucose is said to be present, but it is question- 
able whether this is actually the case under normal conditions (see 
below). As far as the albuminous bodies are concerned which may 
be found in the cerebro-spinal fluid, serum-albumin is said to be 
present only under exceptional conditions, while normally a mixture 



THE EXAMINATION OF THE CEREBROSPINAL FLUID. 529 

of globuliu and albumoses is fouud. The question whether or not 
mucin may also be present is still undecided. 

Under pathologic conditions the amount of albumin may vary 
considerably, and is of some diagnostic importance. According to 
the majority of observers the figure given in the above analysis is 
somewhat too high, and it is questionable whether 1 p. m. may be 
regarded as normal. The lowest values have been obtained in cases 
of chronic hydrocephalus (traces only), meningitis serosa (0.5 to 
0.75 p. m.), and tumors of the brain (traces to 0.8 p. m.), while the 
largest amounts have been found in chronic hydrocephalus, the 
result of hyperemia (1 to 7 p. m.), and tubercular meningitis (1 to 
3 p. m.). 

Lichtheim claims to have found glucose — by means of the phenyl- 
hydrazin test — in all cases of tumor which he examined. In cases 
of tubercular meningitis, on the other hand, a positive result was 
only exceptionally obtained. Quincke also reports that he was able 
to demonstrate the presence of sugar whenever the liquid obtained 
was sufficient in amount for the necessary tests. Unfortunately, 
however, he does not detail his cases. 

The experience of other observers does not agree with that of 
Lichtheim and Quincke, and Fiirbringer, who has thus far reported 
the largest number of spiual punctures, has found sugar in only two 
cases of diabetes associated with tuberculosis. 

Microscopic Examination. The microscopic examination of the 
fluid withdrawn by spinal puncture is most important. 

Under normal conditions, as well as in cases of tubercular menin- 
gitis, tumor, abscess, acute and chronic hydrocephalus, only a few- 
leucocytes and endothelial cells from the subarachnoid spaces are 
usually found, enclosed in extremely delicate meshes of fibrin. In 
purulent meningitis, on the other hand, leucocytes are present in 
large numbers, and in some instances pure pus may even be obtained. 

Most important from a diagnostic standpoint is the fact that patho- 
genic micro-organisms may be found. Lichtheim, Fiirbringer, Frey- 
han, Dennig, and Friinkel were thus able to demonstrate the presence 
of tubercle bacilli in a fairly large number of cases of tubercular 
meningitis. Other observers, it is true, have been less fortunate, 
but the fact that Fiirbringer found tubercle bacilli in thirty cases 
out of thirty-seven is certainly encouraging. In order to examine 
for tubercle bacilli the fluid should be allowed to stand until a slight 
coagulum has formed, when the fine spider-web-like threads of fibrin 

34 



530 CLINICAL DIAGNOSIS. 

are transferred to a cover-slip, spread oat in as thin a layer as pos- 
sible, and stained as described in the chapter on Sputum. If a cen- 
trifugal machine be available, the examination may, of course, be 
made at once, and the chances of finding the bacilli are undoubtedly 
much greater. In every case a number of specimens should be pre- 
pared before the search is abandoned. A positive result only is of 
value. 

In cases of purulent meningitis associated with median otitis 
Lichtheim was repeatedly able to demonstrate the presence of strep- 
tococci, and in some instances of the diplococcus pneumoniae. The 
latter organism, as also the staphylococcus pyogenes aureus and 
albus, has been found in cases of epidemic cerebro-spinal men- 
ingitis. 



CHAPTER XI. 

THE SEMEN. 

DEFINITION. 

The ejaculated semeu is a mixture of the secretions furnished by 
the testicles, the prostate gland, the seminal vesicles, and the glands 
of Cowper. 

GENERAL CHARACTERISTICS. 

Semen is white or slightly yellowish in color, semi-fluid, sticky, 
and of an opaque, non-homogeueous, milky appearance, which is 
due to the presence of white, opaque islets floatiug in the otherwise 
clear fluid ; these consist almost entirely of the specific morpho- 
logic elements of the semen, the spermatozoa. Its odor, strongly 
resembling that of fresh glue, is very characteristic, and is owing 
to the presence of spermin. It is generally attributed to an admix- 
ture of prostatic fluid, as the semen obtained from the vasa defer- 
entia is odorless. According to Robin, however, this odor is only 
produced at the moment of ejaculation, and cannot be ascribed to 
any single one of the secretions present. The reaction of human 
semen is slightly alkaline, and its specific gravity is greater than 
that of water, in which it readily sinks. 

CHEMISTRY OP SEMEN. 

Curiously, no accurate analyses of human semen or of mamma- 
lian semen have been made, and only the old analyses of Vauquelin 
and Kollicker can be given. 





Man. 


Horse. 


Ox. 


Water 


. 90 


81.9 


82.1 


Albuminous material \ 




16.45 


15.3 


Extractives . >- 


. 6 




Ethereal extract ) 




2.2 


Mineral material 


. 4 


1.61 


2.6 



The mineral matter consists largely of calcium phosphate. 

If semen be kept for any length of time, or if it be slowly evapo- 



532 



CL IS 7 CAL I) I A GXOSLS. 



rated, crystal- of spermin will separate out. These have been shown 
to be chemically identical with the phosphate of ethvlenimin. 
C-H, SR . and "hence with the so-called Cnareot-Levden ervstals 



=o irecpaentiy seen m astnmatic sputa and in tn 
patients. 



;eun&eniie 



MICROSCOPIC EXAMINATION OF THE SEMEN. 

Upon m : ::e . ori: examination normal semen is seen to contain 
innumerable, actively moving, thread-like bodies, measuring from 
50 ft. to 60 jj. in length, the spermatozo These con-:-: of n egg- 

shapefi head, wh-ii ; —n from above. Z y. to o c in length, the 
broader end bein^ .".:: ;;:-:'. .-.: .:'.". a mi:l:;le portion. 4 c. to 6 /j 
in length, with which the head is united by i Her eni ; and 

a posterior piece or tail, inoo waioa :':.-. ru ... le piece graduallv fades 
Fig. 126). 




Human semen- a. Spermatozoa. 6. Cylindrical 

granules, d. Squamous epithelium from the nret 

puscles. /. Spermatic crystals, g. Hyaline globules 

In addition to the spermatozoa a 
derived from the seminal vesicles, no 

an albuminous nature, some testicular 
lecithin-corpuscles, and so-called pr 
which at first sight resemble starch- 
to their concentric striations; a Few 
red corpuscles may also be found. 



seen, 



PATHOLOG-Y OF THE SEMEN. 

The study of the semen has as yet received out lit! 
from clinicians, and gynecologists frequently u ol:l the 



attenti . o 

e res o on- 




THE SEMEN. 533 

sible for sterility where an examination of the husband's semen would 
— according to Kehrer, in 40 per cent. — reveal an absence of sperma- 
tozoa, constituting the condition usually spoken of as azoosperma- 
tism. This may be temporarily observed following venereal excesses, 
when the fluid finally ejaculated is almost entirely of prostatic origin ; 
it then possesses no significance, but persistent azoospermatism must 
of necessity be associated with sterility. 

Cases have been recorded in which, notwithstanding the presence 
of spermatozoa and otherwise normal sexual conditions in both hus- 
band and wife, sterility nevertheless existed, but in which it was 
observed that the spermatozoa lost their motile power almost imme- 
diately after ejaculation, while under normal conditions it is a well- 
known fact that following intercourse actively moving spermatozoa 
may be found in the vagina after many hours, days, or even weeks. 

Whenever it is deemed advisable to make an examination of the 
semen, this should be done immediately following ejaculation, or as 
short a time as possible at least be allowed to elapse, and note be 
taken, not only of the presence, but also of the motility of the sperma- 
tozoa, a drop of the semen being mixed with a drop of normal (0.6 
per cent.) saline solution, and at once examined with the microscope. 

THE RECOGNITION OP SEMEN IN STAINS. 

In medico-legal cases the physician may be called upon to decide 
whether or not certain stains on the linen are caused by spermatic 
fluid, whether or not a rape has been committed, etc. In such cases 
it is frequently only necessary to examiue a drop of the vaginal fluid 
in order to arrive at a positive result at once. At other times, how- 
ever, recourse must be had to the following method: A fragment of 
the linen or scrapings from the vulva or vagina are placed in a 
watch-crystal aud allowed to soak for at least oue hour in from 27 
to 30 per cent, alcohol, when a bit of the material is teased in a 
solution of eosin in glycerine (1 : 200), and examined. The heads 
of the spermatozoa are thus stained a deep red, while the tails, 
which are often found broken, exhibit a pale rose-tint, and can 
readily be distinguished from any vegetable fibres present, which 
do not take up the stain at all. A positive statement can thus be 
made in every case, even after months or years, as the spermatozoa 
not only resist the action of reagents, but also the process of putre- 
faction, probably owing to the greater proportion of mineral matter 



534 CLINICAL DIAGNOSIS. 

which enters into their composition, and which insures the preserva- 
tion of their form. Instances have been recorded in which it was 
possible to demonstrate the presence of spermatozoa in stains after 
eighteen years. 

The test recently described by Florence has already attracted much 
attention, and may be recommended in doubtful cases. It is based 
upon the observation that very characteristic crystals of iodospermin 
are formed when spermatic fluid is treated with a solution of iodo- 
potassic iodide, especially rich in iodine. The reagent is composed 
of 1.65 gramme of pure iodine and 2.54 grammes of potassium 
iodide, dissolved in 26 grammes of water. When a drop of this 
solution is added to a drop of spermatic fluid or an aqueous extract 
of a seminal stain, dark brown crystals of iodospermin separate out 
at once and may be readily recognized uuder the microscope. They 
occur in the form of long rhombic platelets, or fine needles, often 
grouped in rosettes, but also occurring singly or as twin crystals. 
The examination with the microscope should be made at once after 
the addition of the reagent, as the crystals gradually disappear on 
standing. 

As the reaction may also be obtained in cases of azoospermatism, 
and with pure prostatic secretion, while a negative result is obtained 
with the fluid from spermatoceles, it is manifest that the test is not 
applicable for the determination of the presence or absence of sper- 
matozoa pro se. This fact, however, would rather make the test 
more valuable than otherwise. 

Posner states that he obtained the same crystals when the test was 
applied to a glycerin extract of ovaries, an observation which cannot 
be surprising, as the ovaries, like the testes and prostatic gland, are 
rich in spermin. Negative results were reached with putrefying 
semen. 

The author found that upon the addition of a drop of a 0.5 per 
cent, alcoholic solution of dimethyl-amido-azo-benzol to a drop of 
spermatic fluid, the heads of the spermatozoa are stained a distinct 
blue, while the neck and tail remain unstained. 



CHAPTER XII. 

VAGINAL DISCHARGES. 



GENERAL CHARACTERISTICS. 

The secretion which is normally furnished by the vaginal glands 
is small in amount, and just sufficient to keep the mucous membrane 
moist. It is a clear or somewhat milky-looking, semi-liquid mate- 
rial, in which numerous epithelial laminae, which have been thrown 
off during the normal process of desquamation, may be found. It 
has been stated that the reaction of the vaginal secretion in virgins 
is invariably acid, while an alkaline reaction is the rule in the de- 
florees. During pregnancy, however, the secretion is probably 
always acid. In 500 cases, which Kroenig examined in this direc- 
tion, an alkaline reaction was never observed. 



Fig. 127. 




Vaginal secretion : a, mucous corpuscles; b, vaginal epithelium ; c, epithelium from vulva. 

Microscopically numerous epithelial cells, mucous corpuscles, a 
few large, mononuclear leucocytes, cellular detritus, and bacteria are 
found. (Fig. 127.) Doederlein has described a non-pathogenic 
bacillus or a group of bacilli, which are characterized by the fact 
that they give rise to marked acid fermentation of sugar, and he 
regards these organisms as the only ones which are constantly present 
in the normal vagina. Kroenig and Menge, however, state that they 



536 CLISICAL DIAGNOSIS. 

are often absent. They have found, on the other hand, that there 
are various bacilli and coeei present under normal conditions, which 
belong to the class of obligatory anaerobes and are likewise non- 
pathogenic. Unfortunately they have not described these organisms 
in detail. Xear the outlet they further found bacteria which can 
be cultivated upon alkaline aerobic culture media, but which are 
usually absent in the upper portion of the vagina. 

It is important to note that various diplococci may also be found 
under normal conditions, aud care should be taken not to confound 
these with the gonococcus. Like the gonococcus, they are unfortu- 
nately decolorized by (Tram's method. If the various characteristics 
of the former be borne in mind, however, mistakes can always be 
avoided. In married females, and in children especially, it will 
probably always be best to make the diagnosis of gonorrhoea only 
when the gonococcus has been isolated by cultivation. 

The question whether or not pathogenic bacteria may occur in the 
normal vagina of pregnant or non-pregnaDt women maybe answered 
in the affirmative, although it must be admitted that with the excep- 
tion of the cronococcus thev are not often found. The vaginal secre- 
tion has been shown to possess most powerful bactericidal properties, 
so that pathogenic organisms, even if they are artificially introduced 
into the vagina, are rapidly killed. Kroenig thu3 found that the 
bacillus pyocyaneus disappears from the vagina of pregnant women 
in from ten to thirty hours, the staphylococci in from six to thirty- 
six hours, and the streptococcus pyogenes within six hours. Impor- 
tant from a practical standpoint is the fact that the bacteria disap- 
peared less rapidly when irrigation of the vao-ina with water or even 
antiseptics was employed. 

Of animal parasites the trichomonas- vaginalis is apparently the 
only one which may be encountered in the vaginal discharge. The 
organism is identical with the trichomonas found in the feces and in 
the urine. In this country it is rarely observed, while it is decidedly 
common among the peasant population of Central Europe. As 
far as is known the organism is of no pathologic significance, and 
may occur both under normal and pathologic conditions. From 
a medico-leg il standpoint, however, its presence may not be unim- 
portant, as cases are on record in which trichomonades have been 
confounded with spermatozDa. Such a mistake, in the writer's judg- 
ment, can ouly occur when the observer is entirely without micro- 
scopic training. In doubtful cases the test of Florence may be 



VAGINAL DISCHARGES. 537 

advantageously employed (see p. 534). Or the specimen may be 
stained with dimethvl-amido-azo-benzol (0.5 per cent, alcoholic solu- 
tion), when the heads of the spermatozoa will exhibit a blue color, 
while the body of the trichomonas is stained yellow. 

VAGINAL BLENORRHCEA. 

In physiologic conditions an increased vaginal secretion is observed 
during sexual excitement, especially during coitus, just preceding 
and at the beginning of the process of menstruation and during 
pregnancy, when a profuse blenorrheea is frequently seen, which 
often assumes a virulent character. The secretion under such con- 
ditions readily becomes purulent. When not depending upon a 
gonorrhceal infection the secretion is thicker than normal, white and 
creamy. At times also the vaginal catarrh observed in pregnancy 
is complicated with mycosis, when white or yellowish-gray patches 
may be seen at the orifice of the vagina; the latter may, indeed, 
even be filled with particles which consist entirely of fungi. 

MENSTRUATION. 

At the beginning of menstruation, as has been pointed out above, 
an increase in the amount of vaginal secretion is observed, in which 
leucocytes, prismatic epithelial cells coming from the uterus, as well 
as the usual vaginal cells, may be seen upon microscopic examina- 
tion. Later the secretion becomes sanguinous in character, and 
finally only epithelial cells, leucocytes, and granular detritus are 
encountered, the cells usually showing evidence of fatty degenera- 
tion. The amount of blood lost at each menstrual period amounts 
to about 200 grammes in perfectly healthy females. 

THE LOCHIA. 

The lochia during the first day following parturition are red in 
color, the lochia rubra, and emit the characteristic sanguinous odor. 
At this time a microscopic examination will reveal an abundance of 
red corpuscles, some leucocytes, and a variable number of epithelial 
cells, which are almost exclusively of vaginal origin. On the second 
and third days the number of red corpuscles diminishes while the 
leucocytes increase in number. Still later the diminution in the red 



53 S CLINICAL DIAGNOSIS. 

and the increase in the white corpuscles becomes more marked, the 
discharge at the same time assuming a grayish or white color, until 
about the tenth day the red corpuscles have almost entirely disap- 
peared, while the leucocytes and epithelial cells are quite abundant. 
Finally, the secretion becomes thicker, mucoid, and milky-white in 
color — the lochia alba, which condition may persist for from three to 
four weeks in nursing-women, and still longer in those who do not 
nurse, until at last the normal secretion is again observed. Numerous 
bacteria are encountered in the lochia, and it is curious to note that 
among these pus-organisms are quite constantly present, without 
giving rise to any symptoms. When a portion of the placenta or 
membranes has been retained the lochia soon give off a fetid odor, 
and assume a dirty brownish color : the retention of blood-clots alone 
may also produce this result. In such cases the lochia swarm with 
bacteria of all kinds. 

VULVITIS AND VAGINITIS. 

In cases of vulvitis and vaginitis a marked increase is observed in 
the number of cellular elements, both leucocytes and epithelial cells, 
the character of the latter depending, of course, essentially upon the 
portion of the genital tract affected. Bed corpuscles are also met 
with at times, their number generally bearing a direct relation to the 
intensity of the inflammatory procese. In some instances epithelial 
casts of the entire vagina have been observed, constituting the con- 
dition which has been termed vaginitis exfoliativa. The disease, 
however, is very rare. 

The discharge of large amounts of pure pus through the vagina 
points to perforation of an abscess of the genital organs or of the 
neighboring structures into the uterus or the vagina, but is of rare 
occurrence. Much more common is the discharge of fecal matter 
or of urine through this channel, indicating the existence of a 
va^ino-reetal or va^ino-vesical fistula. 

MEMBRANOUS DYSMENORRHEA. 

While ordinarily, during menstruation, shreds of desquamated 
uterine lining are frequently encountered, it is rare to meet with 
large pieces or complete casts of the uterus, the elimination of which 
is usually associated with the symptoms of a severe dysmenorrhoea, 



VAGINAL DISCHARGES. 



539 



constituting the condition geuerally spoken of as membranous (h/x- 
menorrhcea. 

CANCER. 

While the diagnosis of a malignant growth of the uterus has prob- 
ably never been based upon a microscopic examination of the vaginal 
discharge, it may be mentioned that such, however, is possible, as 
fragments of an epithelioma of the cervix, for example, may fre- 
quently be detected upon microscopic examination. (Fig. 128.) 

Fig. 128. 




Vaginal secretion from a case of epithelioma of the cervix uteri. 

GONORRHOEA. 

Very important is the examintion of both vaginal and urethral 
discharges in suspected cases of gonorrhoea for the presence of gouo- 
cocci, as it is practically impossible to diagnose this condition posi- 
tively in any other manner. Care should be taken, however, not 
to confound the diplococci, which may be normally present in the 
urethra and vagina, with the gonococcus (see chapter on Urine). 



ABORTION. 

In cases of abortion it is often possible to discover chorion villi 
in the blood-clots which have been expelled, presenting their charac- 



\~: 



::3":;i: zz±c-y: m 



teristie capillary networks J:,: "_ . : -_ 

of advanced fatty degeneration. Iiaporteunifc also from a, 

point of view is the preset : t : I _ IS' ~ 






_'r-:.iui- :■-_£ 



characterized by th&r large 
like form, and ifoeir 






CHAPTER XIII. 

THE SECRETION OF THE MAMMARY GLANDS. 

THE SECRETION OF MILK IN THE NEWLY BORN. 

A secretion from the mammary glands in the male is only 
observed in the newly born, with the exception of the very lare 
cases where adult males were known to suckle infants. The fluid 
in question, which may also be obtained from the female infant, is 
termed " Hexenrnilch" (witches' milk) by the Germans. Quali- 
tatively it has the same composition as milk, but may manifest con- 
siderable quantitative variations. 



COLOSTRUM. 

Aside from those curious instances in which a secretion of milk 
has been observed in non-pregnant adult women, mammary activity 
is essentially connected with the physiologic phenomena of preg- 
nancy and parturition. Often as early as the third month a small 
drop of a serous-looking fluid can be obtained from the nipple by 
pressure upon the breasts. Immediately after birth a variable 
amount of fluid is secreted, which is watery, semi-opaque, mucil- 
aginous, and of a yellowish color. To this secretion as well as to 
that observed during pregnancy the term colostrum has been applied. 
It is distinguished from true milk by its physical characteristics 
and by the presence of a greater proportion of sugar and salts. The 
fluid, moreover, is coagulated by boiling. An idea may be formed 
of its chemical composition from the appended tables : 







4 weeks before birth. 


17 days be- 
fore birth. 

851.7 


9 days be- 
fore birth. 


24 hours 
after birth 


2 days 
after birth. 




' 


Water 




945. 2 852. 


858.8 


843.0 


867.9 


Solids 




54.8 148.0 


148.3 


111.2 


157.0 


132.1 


Casein 
Albumin 






28. 8 69. 


74.8 


80.7 




21.8 


Fat . 




7.3 41.3 


30.2 


28. •"» 




48.6 


Lactose 




17. 3 39. 5 


43.7 


36.4 




61.0 


Salts . 




4.4 4.4 


4.5 


5.4 


" 






542 CLINICAL DIAGNOSIS. 

Upon microscopic examination minute fat-droplets, a few leuco- 
cytes, some epithelial cells, and so-called colostrum-corpuscles are 



Fig. 131. 

©IP- - 

Colostrum of a woman in sixth month of pregnancy. (Eye-piece III., obj. 8 a, Reichert.) 

(v. Jaksch.) 

found. The latter are highly refractive bodies of irregular size, 
whose interior is filled with fatty granules. (Fig. 131.) 



THE SECRETION OP MILK PROPER IN THE ADULT 

FEMALE. 

The secretion of milk proper usually begins about the third day 
following parturition, and may continue for a variable length of 
time. On the one hand, the amount of milk secreted may be so 
small as to be insufficient for the wants of the child, so that lacta- 
tion may have to cease after several days. On the other hand, 
women are not infrequently seen who nurse children for two years 
or even longer. Usually, however, infants are nursed until six 
or seven teeth have appeared, which period varies with the indi- 
vidual child, averaging about the eleventh month. 

HUMAN MILK. 

Human milk is of a bluish color, in this respect differing from 
the milk of cows. Its reaction is alkaline. The specific gravity 
may vary between 1.026 and 1.035, one between 1.028 and 1.034 
being the most common. The amount of milk secreted in twenty- 
four hours varies from 500 to 1500 c.c. Microscopically it is a fairly 
homogeneous emulsion of fat, being practically destitute of cellular 
elements. From the following table an idea may be formed of its 
chemical composition : 



THE SECEETION OF THE MAMMARY GLANDS. 



543 





Biehl. 


Gerber. 


Christenn. 


Pfelflfer. 


Pfeiffer. 
890. 6 


Water 


876. 


891.0 


872. t 


892. 


Solids 


124. 


109.0 


127.6 


108.0 


109.4 


Albumin . 


22.10 


17.90 


19.00 


16.13 


17.24 


Fat .... 


38. 10 


33.00 


43.20 


32.28 


29.15 


Lactose . 


60.90 


53.90 


59.80 


57.94 


59.92 


Salts . 


2.90 


4.20 


2.60 


1.65 


2.09 



Moixlesde 
Leon. 



877.9 

25.30 

38.90 

55.40 

2.50 



Upon comparing this table with the following analysis of cow's 
milk, it will be seen that the latter usually contains more albumin 
and less sugar than human milk. Human milk, moreover, is 
relatively deficient in mineral matter and especially in CaO and 

PA: 

Water 874.2 

Solids 125.8 

Casein 28 - 8 }34 5 

Albumin ...... . 5.3 > 

Fat 36.6 

Lactose 48. 1 

Salts 7.1 

The albumins found in milk-plasma are casein, lacto-globulin, 
and lactalbumin. It is claimed by numerous observers that the 
casein of human milk differs from that obtained from cow's milk. 
The casein-coagula in human milk are not so large and dense as 
those observed in cow's milk. Human casein, moreover, is not so 
readily precipitated by acids and salts ; it does not always coag- 
ulate upon the addition of rennet ferment, and while it can be pre- 
cipitated by the gastric juice it is readily dissolved by an excess. 
Although accurate analyses of human casein are not accessible, it is 
probable that the two forms are not identical (Hammarsten). 

The question whether or not normal human milk contains micro- 
organisms may now be answered in the affirmative. There can 
be no doubt, however, that the milk as it is secreted by the healthy 
gland is sterile, but upon passing along the lacteal ducts in the 
nipple it is ahvays contaminated by the staphylococcus epidermidis 
albus ( Welch). This micro-organism must be regarded as a con- 
stant inhabitant of the skin, and is the only one of the cutaneous 
bacteria which regularly penetrates into the deeper layers of the 
epidermis and into the glandular appendages of the skin. It is 
thus at once apparent why this organism is so constantly met with, 



OU 



CLINICAL DIAGNOSIS. 



and practically the only one that is found in normal human milk. 
Exceptionally only the staphylococcus pyogenes aureus is found. 



Tig. 132. 



I 






THE MILK IN DISEASE. 

The chemistry of the milk in pathologic conditions has received 
but little attention. It appears, however, that the milk of women 
while ill usually contains less fat, and that the 
proportion of lactose is diminished. In cases of 

jaundice the presence of bile-pigment and of biliary 
acids has not as yet been satisfactorily demon- 
strated. In cases of mammary tumors bloody 
secretion has been observed in rare cases, the nip- 
ple itself being intact. 

Microscopically an admixture of leucocytes is 
observed in various diseases of the breast, and 
especially in cases of abscess. Of pathogenic 
micro-organisms streptococci may be found in 
cases of puerperal fever ; more commonly, how- 
ever, they are absent. The typhoid bacillus has 
been occasionally seen in cases of typhoid fever, 
and pneumococci have been obtained from the 
milk of pregQant women affected with lobar pneu- 
monia. The important question whether or not 
tubercle bacilli are eliminated through the milk 
in cases of phthisis cannot be definitely answered. 
In cows such an occurrence is certainly quite 
common, even when there is no demonstrable 
tuberculosis of the udder, while they are con- 
stantly present when this is diseased. As far as 
the writer has been able to ascertain they have 
never been found in human milk. 

A blue and red color has at times been observed 
in the milk of cows, owing to the presence of the 
bacillus cyanogenus and the micrococcus prodi- 
giosus, respectively. 

A chemical examination of the mother's milk 
is often of the greatest importance, and should 
always be made whenever it is apparent that the 
nutrition of the baby is below normal. Most 
m^ee, ~ = "" valuable dietetic suggestions may thus be obtained. 




THE SECRETION OF THE MAMMARY GLANDS. 



545 



In other cases, as when the mother is unwilling or unable to nurse 
her chilil beyond a certain period, a knowledge of the composition 
of her milk will enable the physician to give specific instructions 
regarding the proper modification of cow's milk. If a wet-nurse is 
to be employed, her milk should likewise be examined. 

Most important is the determination of the specific gravity and of 
the amount of fat. The former may vary between 1.029 and 1.033. 
The amount of fat should not be less than 3 per cent. 

Determination of the Specific Gravity. 
The specific gravity is best determined with the lactodensimeter 
of Quevenue. (Fig. 132.) As the instrument is graduated for a 
temperature of 60° F., it is necessary to correct the specific gravity 
whenever the temperature rises above or falls below this point. In 
the following tables the corrected specific gravity may be found 
corresponding to temperatures ranging from 46° to 75° F. : 

Corrections for Temperature. 









Degrees of thermometer (Fahrenheit). 


Specific 
gravity. 


















16 


47 


4S 


49 


50 


51 


52 


53 


1020 


19.0 


19.1 


19.1 


19.2 


19.2 


19.3 


19.4 


19.4 


1021 


20.0 


20.0 


20.1 


20.2 


20.2 


20.3 


20.3 


20.4 


1022 


21.0 


21.0 


21.1 


21.2 


21.2 


21.3 


21.3 


21.4 


1023 


22.0 


22.0 


22.1 


22.2 


22.2 


22.3 


22.3 


22.4 


1024 


22.9 


23.0 


23.1 


23.2 


23.2 


23.3 


23.3 


23.4 


1025 


23.9 


24.0 


240 


24.1 


24.1 


24.2 


24.3 


24.4 


1026 


24.9 


24.9 


25.0 


25.1 


25.1 


25.2 


25.2 


25.3 


1027 


25.9 


25.9 


26.0 


26.1 


26.1 


26.2 


26.2 


26.3 


1028 


26.8 


26.8 


26.9 


27.0 


27.0 


27.1 


27.2 


27.3 


1029 




27.8 


27.9 


28.0 


28.0 


28.1 


28.2 


28.3 


1030 


28.7 


28.7 


28.8 


28.9 


29.0 


29.1 


29.1 


29.2 


1031 


29.6 


29.6 


29.7 


29.8 


29.9 


30.0 


30.1 


30.2 


10*2 


30.5 


30.5 


30.6 


30.7 


30.9 


31.0 


31.1 


31.2 


1033 


31.4 


31.4 


31.5 


31.6 


31.8 


31.9 


32.0 


32.1 


1034 


32.3 


32.3 


32.4 


32.5 


32.7 


32.9 


33.0 


33.1 


1035 


33.1 


33.2 


33.4 


33.5 


33.6 


33.8 


33.9 


34.0 







54 


55 


19.5 


19.6 


20.5 


20.6 


21.5 


21.6 


22.5 


22.6 


23.5 


23.6 


24.5 


24.6 


25.4 


25.5 


26.4 


26.5 


27.4 


27.5 


28.4 


28.5 


29.4 


29.4 


30.3 


30.4 


31.3 


31.4 


32.3 


32.4 


33.2 


33.3 


34.2 


34.3 



Specific 
gravity. 



1020 
1021 
1022 
1023 
1024 
1025 
1026 
1027 
1028 
102!) 
1030 
1031 
1032 
1033 
1034 
1035 



Degrees of thermometer (Fahrenheit). 



56 


57 


58 


59 


60 


61 


62 


63 


64 
203 


19.7 


19.8 


19.9 


19.9 


20.0 


20.1 


20.2 


20.2 




20.8 


2>.9 


20.9 


21.0 


21.1 


21.2 


21.3 


21.4 


21.7 


21.8 


21.9 


21.9 


22.0 


22.1 


22.2 


22.3 


22.4 


22.7 


22.8 


22.8 


22.9 


23.0 


23.1 


23.2 


23.3 


23.4 


23.6 


23.7 


23.8 


23.9 


24.0 


24.1 


24.2 


24.3 


24.4 


24.6 


24.7 


24.8 


24.9 


25.0 


25.1 


25.2 


25.3 


25.4 


25.6 


35.7 


25.8 


25.9 


26.0 


26.1 


26.2 


26.3 


26.5 


26.6 


26.7 


26.8 


26.9 


27.0 


27.1 


27.3 


27.4 


27.5 


27.6 


27.7 


27.8 


27.9 


28.0 


28.1 


28.3 


28.4 


28.5 


28.6 


28.7 


28.8 


28.9 


29.0 


29.1 


29.3 


29.4 


29.5 


29.6 


29.7 


29.8 


29.9 


30.0 


30.1 


30.3 


30.4 


30.5 


30.5 


30.6 


30.8 


30.9 


31.0 


31.2 


31.3 


31.4 


31.5 


31.5 


31.6 


31.7 


31.9 


32.0 


32.2 


32.3 


32.5 


32.6 


32.5 


32.6 


32.7 


32.9 


33.0 


33.2 


33.8 


33.5 


33.6 


33.5 


33.6 


33.7 


33.9 


34.0 


34.2 


34.3 


34.5 


34.6 


34.5 


34 6 


34.7 


34.9 


35.0 


35.2 


35.3 


35.5 


35.6 



65 



20.4 
21.5 
22.5 
23.5 
24.5 
25.5 
26.6 
27.6 
2S 6 
29.6 
30.7 
317 
32.7 
33.8 
34 - 
35.. S 



:;.-, 



546 



CLINICAL DIAGNOSIS. 



Specific 






Degrees of thermometer (Fahrenheit) 








gravity. 














1 










66 


67 


68 


69 


70 


71 


72 


73 


74 


75 


1020 


20.5 


20.6 


20.7 


20.0 


21.0 


21.1 


21.2 


21.3 


21.5 


21.6 


1021 


21.6 


21.7 


21.8 


22.0 


22.1 


22.2 


22.3 


22.4 


22.5 


22.6 


1022 


22.6 


22.7 


22.8 


23.0 


23.1 


23.2 


23.3 


23.4 


23.5 


23.7 


1023 


23.6 


23.7 


23.8 


24.0 


24.1 


24.2 


24.3 


24.4 


24.6 


24.7 


1024 


24.6 


24.7 


24.9 


25.0 


25.1 


25.2 


25.3 ! 


25.5 


25.6 


25.7 


1025 


25.6 


25.7 


25.9 


26.0 


26.1 


26.2 


26.4 


26.5 


26.6 


26.8 


1026 


26.7 


26.8 


27.0 


27.1 


27.2 


27.3 


27.4 1 


27.5 


27.7 


27.8 


1027 


27.7 


27.8 


28.0 


28.1 


28.2 


28.3 


28.4 


28.6 


28.7 


28.9 


1028 


28.7 


28.8 


29.0 


29.1 


29.2 


29.4 


29.5 


29.7 


29.8 


29.9 


1029 


29.8 


29.9 


30.1 


30.2 


30.3 


30.4 


30.5 ' 


30.7 


30.9 


31.0 


1030 


30.8 


30.9 


31.1 


31.2 


31.3 


31.5 


31.6 


31.8 


31.9 


32.1 


1031 


31.8 


32.0 


32.2 


32.2 


32.4 


32.5 


32 6 


32.8 


33.0 


33.1 


1032 


32.9 


33.0 


33.2 


33.3 


33.4 


33.6 


33.7 


33.9 


34.0 


34.2 


1033 


33.9 


34.0 


34.2 


34.3 


34.5 


34.6 


34.7 


34.9 


35.1 


35.8 


1034 


34.9 


35.0 


35.2 


35.3 


35.5 


35.6 


35.8 


36.0 


36.1 


36.3 


1035 


35.9 


36.1 


36.2 


36.4 


36.5 


36.7 


36.8 


37.0 


37.2 


37.3 



The Estimation of Fat. 

The estimation of the fat is most conveniently made by means of 
the lactoscope of Feser, shown in Fig. 133. Milk is drawn into 



Fig. 133. 




Feser's lactoscope. 



THE SECRETIOS OF THE MAMMARY QLAM>s. 547 

the pipette up to the mark M, when it is emptied into the cylinder 
C. The pipette is then rinsed with water and the washings added 
to the milk. While shaking, water is added, until the black lines 
upon the milk-colored glass plug A can just be discerned. The 
figure upou the right of the scale which is reached by the mixture 
will at once indicate the percentage-amount of fat, while the number 
upon the left indicates the amount of water in c.c. that has been 
added. 



INDEX 



ABOKTIi >\. vaginal discharge in, 539 
Abscess of the liver with perforation 
into the lung, 270 
pulmonary, 269 
Absorption, rate of, in the stomach, 176 
Acetic acid. 162, 194 

fermentation, 1G2 
tests for, 163, 194 
Acetonemia, 53 
Acetone in the blood, 53 

in the gastric contents, 166 

in the urine, 453 

quantitative estimation of, 456 

tests for, 455 
Acetonuria, 53, 453 
Acetvlene-poisoning, blood changes in, 

38 
Acholic stools, 199 
Achroodextrin, 102, 149 
Acid, acetic, 162, 163, 194 

benzoic, 364 

butyric, 162, 163, 194 

capric, 193 

caproic, 193 

carbolic, 316, 445 
tests for, 452 

diacetic, 457 

diazo-benzene-sulphonic, 449 

formic, 194 

hippuric, 362 

homogentisinic, 446 

hydrochloric, 125 

isobutvric 193 

lactic/ 153, 458 

oleic, 195 

oxalic, 373 

oxaluric, 373 

oxybutyric, 458 

palmitic, 193, 195 

phosphoric, 305 

picric, 401, 40-3 

propionic, 194 

stearic, 193, 195 

succinic, 523 

sulphuric, 316 

uric, 349 

uroleucinic, 4-15 

valerianic, 193 
Acidity of the urine, determination of, 

292* 
Acids, organic, in the gastric contents, 161 



Actinomyces hominis, 264 
Actinomycosis, 108 264 

of the mouth, 108 
Acute yellow atrophy, urine in, 325 
Adenin in the urine, 370 
a-granulations of Ehrlich, 64 
Albumin, amount of, 389 

in the feces, 234 

in the gastric contents, 147 

in the urine, 376 

quantitative estimation of, 402 

tests for, 395 
boiling, 399 
nitric acid, 396 
picric acid, 401 
potassium ferrocyanide, 400 
Spiegler's, 402 
trichloracetic acid, 401 

special test for serum-albumin, 402 
for serum-globulin, 405 
Albuminimeter, Esbach's, 403 
Albuminuria, 376 

accidental, 388 

colliquative, 383 

cyclic, 378 

Da Costa's, 377 

digestive, 387 

febrile, 381 

functional. 378, 380 

hematogenous, 379, 385 

in organic diseases of the kidneys, 
380 

intermittent, 378 

mixed, 388, 390 

neurotic, 386 

physiologic, 376 

postural, 378 

referable to circulatory disturbances, 
384 
to impeded outflow of urine, 385 

toxic, 386 

transitory. 378 
Albumoses in the blood, 45 

in the gastric contents, 147 

in the urine, 389 

tests for, 151, 406 
Albumosuria, 389 
Alkaline stools, 189, 199 

urine, 290 
Alkalinity of the blood, 21 

estimation of, 22, 24 



550 



INDEX. 



AJkapton in the urine. 445 

Alkaptonuria, 445 

Alloxur bases in the urine, 371 

estimation of, 371 
Aim en's solution, 417 
Alveolar epithelium, 256 ; 
Amido acids, 324 

Ammonia in the gastric contents, 165 
Ammoniacal fermentation 290 — ~~ 

Ammonio-magnesium phosphate, 290. 

469 
Ammonium urate. 4, 9 
Amoeba coli, 210, 241, 259 
Amoeba? in the urine, 510 
Amoebic colitis, 241 
Amorphous hsematoidin, 41, 266, 478 
Amphistomum hominis, 223 
Amphoteric urine. 289 
Amyloid corpuscles in the semen, 532 
Anachlorhydria. 129 
Anacidity. hysterical, 129 
Anaemia, albuminuria in, 386 

blood in, 100 

pernicious, blood-changes in, 100 

simple secondary, 100 
Anchylostomiasis. 208, 226 
Anchylostomum duodenale, 226 
Anguillula intestinalis, 227 

stercoralis. 22 B 
Anguilluliasis/203. 226 
Aniline dyes, classification of, 62 

water, gentian-violet, 109, 262 
Animal gum in the urine, 429 

parasites in the blood, 88 
in the feces, 209 
in the sputum. 258 
Annelides, 224 
Anthxomyia, 209 
Anthracosis of the lung, 272 
Anthrax, bacillus of, 85 
Anuria, 282 

Aromatic oxy- acids, 445 
Aronsohn-Philips r stain, 69 
Ascarides in the feces, 224 

in the urine. 510 
Ascaris lumbricoides, 224 

maritima. 225 
Asiatic cholera, bacillus of, 230 

feces in, 240 
Asthma, bronchial. Charcot-Levden crys- 
tals in, 244. 253,254^269 
Atrophy, gastric, 179 
Aurantia, 63 
Azoospermatism, 533 



BACILLI of Booker, 232 
Bacillus butyricus, 188 
coli communis. 232 
lactis aerogenes, 233 
of anthrax, 85 
of cholera Asiatica. 230 
of diphtheria, 104, 109 



Bacillus of Finkler and Prior, 230 
of glanders, 85 
of influenza, 86 
of Le Sage, 232 
of smegma, 507 

of tuberculosis, methods of staining, 
262 
in the blood, 85 
in the feces, 232 
in the meningeal fluid, 529 
in the milk. 544 
in the mouth, 108 
in the nasal discharge, 244 
in the sputum, 260 
in the urine, 507 
of typhoid fever, in the'blood, 79 
in the feces, 231 
Bacteria in the blood, 79 
in exudates, 518 
in the feces, 187, 228 
in the gastric contents, 173 
in the milk, 544 
in the mouth, 103 
in the nasal secretion, 244 
in the pus, 518 
in the sputum, 260 
in the urine, 504 
in the vagina, 535 
Bacterial decomposition of the urine, 

290 _ 
Bacteriuria, 506 

idiopathic, 509 
Balantidium coli, 216 
Barfoed's reagent. 153 
Basic aniline dyes, 63 

phosphate of magnesium. 471 
Basophilic leucocytes, in the blood, 65 

in the sputum. 254 
Benzoic acid in the urine, 364 
Benzopurpurin test for hvdrochloric 

acid, 133 
Bile-pigment in the blood, 52 
in the feces, 235 
in the gastric contents. 170 
in the urine, 439 
tests for, 441 

Gmelin's, 441 
Huppert's 441 
Bosenbach's, 441 
Bosin's, 441 
Smith's, 441 
Bilharzia haernatobia, 99 
Biliary acids in the blood, 52 
in the feces, 196 
in the urine, 442 
tests for, 197 
concretions, 204 
analvsis of. 205 
Bilirubin. 52," 439, 477 
Bismarck-brown. 262 
Biuret test, 332 ' 
Blood, 17 

acetone in, 53 



INDEX. 



551 



Blood, albumins in, 26, 1 1 

alkalinity of, -1 

bacteriology of, 79 

biliary constituents ill. 52 

carbohydrates in, 45 

cellulose in. 47 

coagulation of, 25 

color of, 17 

-corpuscles, rod, 17, 53 

drying and staining of, 06 

enumeration of, 71, ~- 

t'at in, 50 

fatty acids in, 50 

fibrin in, 12 » *• 

ga-es in, 28 

general characteristics of, 17 
chemistry of, 25 

glycogen in, 47 

in" the feces, 200, 207 

in the gastric contents, 170 

in the sputum, 248, 255 

in the urine, 393, 438 

lactic acid in, 51 

medico-legal test for, 40 

nucleated corpuscles in, 56 

odor of, IS 

parasites in, 79 

parasitology of, 79 

peptone in, 44 

pigments of, 29 

-plasma, 17, 26 

-plates, 71 

proteids in, 44 

protozoa in, 88 

reaction of, 21 

-serum, 26, 27 

-shadows, 490 

solids of, 20 

specific gravity of, 18 

tests for, 40 

guaiacum, 409 
Heller's, 409 

urea in, 48 

uric acid in, 48 

variations in form of corpuscles, 54 
in number of, 54 
in size of, 53 

white (see Leucocytes), 57 

xanthin bases in, 50 
Boas' bulbed stomach-tube, 116 

method for estimating lactic acid, 159 

test for lactic acid. 158 
Boas-Oppler bacillus, 173 
Bodo urinarius, 215 
Bothriocephalus latus, 221 
Bottger's test for sugar, 417 
Brieger's cholera-red reaction, 230 
Bronchial asthma, 269, 244 
Bronchitis, acute, 268 

chronic, 268 

fibrinous, 269 

putrid, 269 
Browning's spectroscope, 43 



Buccal Becretion [see Saliva I, 101 
Butyric acid fermentation, 162 

in tlu> gastric contents, 161 

test for, 163 



CADAVKIMN, 461, 472 
Calcium carbonate, crystals of, 480 
phosphate, crystals of, 470, 471 
sulphate, crystals of, 472 
Calliphora erythrocephala, 210 
Calomel stools, 182 
Cancer of the stomach, 179 
Carbohydrates, digestion of, 149 
in the blood, 45 
in the feces, 235 
in the urine, 409 
tests for, 1 52 
Carbol-fuchsin, 262 
Carbolic acid, estimation of, 453 

tests for, 453 
Carbolo-chloride of iron, test for lactic 

acid, 156 
Carbonic oxide, detection of, 166, 417 

haemoglobin, 38 
Caries of the teeth, 101 
Carnin in the urine, 370 
Casein, digestion of, 148 

in the milk, 543 
Casts, classification of, 492 
examination of, 493 
fatty, 496 
fibrinous, 250 
formation of, 499 
granular, 494 
hyaline, 493 
pus, 486 

significance of, 500 
staining of, 493 
urinary, 492 
waxy, 497 
Catarrh, acute intestinal, 238 
bronchial, 268 
chronic intestinal, 240 
duodenal, 239 
intestinal of infants, 240 
of ileum, 239 
of jejunum, 239 
of large intestine, 239 
Cellulose in the blood, 47 
Cercomonas intestinalis, 214 
Cerebro-spinal fluid, 244, 525 
amount of, 526 
appearance of, 526 
chemical composition of, 528 
examination of, 525 
microscopic examination of, 529 
reaction of, 528 
specific gravity of, 528 
Cestodes, 209 
Chalicosis, 272 

Charcot-Leyden crystals, in the feces, 
185, 208 



552 



ixjjex. 



Charcot Leyden crystals, in the nasal dis 
charge, 24.4 
in the sputum, 254, 265 
Chemical examination of the blood ; 25 
of the buccal secretion, 101 
of cvstic fluids, 521 
of the feces. 189, 234 
of the gastric juice, 120 
::' the milk. 542 
of the pu~. 51 
of the semen, 531 
of the sputum. 2 
of transudates, 513 
of the urine, 294 
Cenomonadina, 212 
Chenzinsky-Plehns stain, 69 
Chloride of zinc solution, 369 
Chlorides in the urine. _ 

:• imation of, 299 

accordingr to Neubauer and 
Salkowski I 3 \ 
Salkowski and Vol- 
hard. . 
direct method. 304 
test for. i 
Chloroform-benzol mixture, 19 
Chlorosis, blood changes in, 100 
Cholaemia, 52 
Cholera Asiatica. 242 

bacillus of. 11 " 
infantum, 240 
nostras. 230. 240 

bacillus of 231 
-red reaction of Brieger. 230 
Cholesterin in the blooi. - v 
in the feces, 195 
in the sputum. 2 
in the urine. 442 
test for. 196 
Choluria. 440 
Chorion villi. 539 

Chromogens in the urine. 429. 432. 438 
Chyluria, 99, 393, 460, 479 
Chymosin. 145 

estimation of, 146 
test for. 146 
Chymosinogen, 145 
estimation of, 147 
test for. 146 
Ciliated epithelium in cysts, 521 

in the sputum, i 7 
Cladothrix. 264 
Coating of the tongue, 107 
Coccidia in the feces. 216 
Coffin-lid crystals. 469. 479 
Colica mucosa. 2 

Colloid concretions in ovarian cysts " 22 
Colostrum, 541 
Comma bacillus, 230 
Concretions, biliarv. 204 
fecal, 204 
intestinal. 2 
pulmonary. 254 



Congo red test, 129 
Conjugate sulphates, 316 
Constipation. 19S. 237 
Copper test for uric acid, 355 
Coproliths, 205 
Corpora amylacea. 532 
Cresol in the feces, 193 

in the urine, 455 
Crystals of bilirubin, 477 

calcium carbonate. 480 

phosphate, 469, 470. 471 
sulphate. 472 

of Charcot-Levden. 185, 208, 244. 
254. 265 

of cholesterin, 28, 195, 196, 266, 442 

of cvstin. 472 

of fatty acids. 266 

of ha?matoidin, 41, 266, 47 S 

of haemin, 39 

of hippuric acid. 471 

of indigo, 434 480 

of leucin, 267. 474 

of magnesium phosphate. 471 

of oxalate of calcium, 267, 468 

of phenyl-glucosazon, 419 

of phosphate of spermin, 531 

of Teichmann, 39 

of triple phosphate, 267, 469, 479 

of tyrosin, 267. 4. 4 

of urate of ammonium, 479 

of uric acid, 465 

of xanthin 47 
Curschmann's spirals, 252 
Cylinders, mucous, 203 240 

urinarv. 443 
Cylindroids, 498 
Cylindruria. 492 
Cysticercus cellulosae, 219 
Cystin, 472 
Cystinuria, 472 
Cysts zolloid 522 

contents of, 521 

dermoid, 510. 522 

fibro cystic 522 

hydatid, 523 

ovarian. 521 

pancreatic, 523 

parovarian, 522 



DAIiAJSTFS haematokrit, 76 
Decidual cells. 540 
^-granulations of Ehrlich, 65 
Denaturization. 147 
Dermoid cysts. 51 C ,522 
Deutero-albumuse. 14^ 
Dextrin in the urine. 42 S 
Dextrose in the urine see Glucose). 
Diabetes. 413 

alternans, 352 

elimination of sugar in, 413 

of urea in, 331 
hepatogenic, 4i4 




IN DUX. 



r>r } :) 



Diabetes, Hirschfeld'e form of, 331, 415 

insipidus, 281, 299 

myogenic, 1 1 I 

pnosphatic, 309 
Diacetic arid in the urine, 457 

test for, 458 
Diaoeturia, 157 

Diamines in the urine, 461, 172 
Diarrhoea, 1 98, 235 
Diathesis, uric acid. 351 
Dia/.o-reaetion (see Ehrlich's reaction), 

447 
Digestion, gastric, 147 

of albumins, 147 

of albuminoids, 149 

of carbohydrates, 149 

of milk, 148 

of native albumins, 147 

products of, 147 
Dilatation of the stomach, 179 
Dimethvl-amido-azo-benzol test, 130 
Diphtheria, 109 

Diplococcus pneumonia?, 81, 104, 263 
Distoma, Buskii, 223 

capense, 99 

conjunctum, 223 

haematobium, 99 

hepaticum, 222 

heterophyes, 223 

lanceolatum. 223 

pulmonale, 259 

rhatonisi, 223 

sibiricum, 223 

spatulatum, 223 

urinse, 459 
Distomiasis, 99 
Donne's pus-test, 486 
Drosophila melanogastra, 210 
Drugs, effect of, on the color of the stools, 

182 
Drysdale's corpuscles, 522 
Dysentery, 240 

amoebic, 241 

tropical, 184 



EARTHY phosphates, 469, 479 
Eberth's bacillus, 79, 231 
Echinococci, 223, 254, 258 
Echinococcus membranes in the sputum, 

254 
e-gran illations of Ehrlich, 64 
Ehrlich's granulations, 62 
reaction, 447 
staining methods, 66 
tri-glycerine mixture, 68 
-acid stain, 68 
Einhorn's bucket, 117 
saccharimeter, 419 
Elastic tissue in the sputum, 250, 257 
Eisner's reaction, 231 
Emerald-green test for hydrochloric acid, 
132 



Enteritis, acute, 238 

chronic, 2 l<» 
membra nosa, 203, 240 
mucosa (see Membranosa), 203, 240 
Enterogenic peptonuria, 390 

Enteroliths. 205 

I'.osin, staining with, 68 

Eosinophilic leucocytes in the blood, 64 

in the sputum, 254 
Epithelial cells, alveolar, 256 
ciliated, 256 

in the buccal secretion, 103 
in the feces, 207 
in the sputum, 254 
in the urine, 481 
in the vaginal secretions, 535 
Eructatio nervosa, 166 
Erythrodextrin, 102, 149 

test for, 152 
Esbach's album inimeter, 403 

method of estimating albumin, 403 
reagent, 402, 403 
Euchlorhydria, 128 
Ewald's modification of Mohr's test for 

hydrochloric acid, 133 
Extractives in the blood, 28 
Exudates, 511, 514 
albumin in, 512 
chyloid, 519 
chylous. 519 
coagulation of, 513 
hemorrhagic, 515 
in cancer, 515 
purulent (see Pus), 516 
putrid, 516 
serous, 514 

specific gravity of, 512 
in tuberculosis, 515 



FAT in the blood. 28, 50 
in the milk, estimation of, 546 
in the urine, 459, 478 
Fatty acids in the blood, 50 

clinical significance, 161 
estimation of. 163 
in the feces, 193 
in the gastric contents, 161 
in the pus, 517, 519 
in the sputum, 266 
in the urine, 459 
mode of formation of, 161 
tests for, 194 
casts, 496 
Febrile acetonuria, 454 
albuminuria. 381 
urobilin, 197, 443 
Fecal matter in the urine, 510 

vomiting, 171 
Feces, 181 

alimentary detritus in, 183, 201 
amount of, 181, 199 
annelides in, 224 



554 



INDEX. 



Feces, blood in, 200, 207 

chemistry of, 189, 234 

color of, 182, 199 

composition of, 189 

consistence of, 182, 198 

crystals in, 185, 208 

examination of normal, 181 

flagellata in, 212 

foreign bodies in, 183 

form of, 182, 198 

gases in, 190 

general characteristics of, 181 

indol in, 191 

insects in, 209, 228 

macroscopic constituents of, 183, 201 

microscopic constituents of, 183, 205 

number of stools, 181, 197 

odor of, 182, 199 

parasites in, 187 
animal, 209 
vegetable, 187, 228 

pathology of, 197 

phenol in, 191 

protozoa in, 210 

reaction of, 189, 199 

skatol in, 191 

technique in examination of, 205 

trematodes in, 222 

vermes in, 217 
Fehling's solution, 416 

test for sugar, 416 
Ferment, milk-curdling, 145 

of saliva, 102 
Fermentation-test for sugar, 417 
Ferments in the gastric juice, 141 

in the urine, 460 
Feser's lactoscope, 546 
Fibrin, 26 

estimation of, 44 

ferment, 26 

in the blood, 26 

in the urine, 393 

test for, 409 
Fibrinogen, 26 
Fibrinoglobuliu, 26 
Fibrinous casts, 250 

coagula in the sputum, 251 

in the urine (see Chyluria) , 393 
Filaria Bancrofti, 97 

diurna, 98 

Mansoni, 97 

nocturna, 98 

sanguinis hominis, 97 

Wuchereri, 97 
Filariasis, 97 

Finkler-Prior bacillus, 230 
Fleischl's haemometer, 32 
Florence's test for semen, 534 
Forceps, cover-glass, 66 
Foreign bodies in the feces, 183 
in the sputum, 254 
in the urine, 510 
Formic acid, detection of, 194 



Frankel's method of determining aciditv 
of urine, 292 
pneumococcus, 81, 104, 263 
Friedlander's bacillus, 84 
Furfurol test for bile acids, 197 



GABBETT'S staining method, 262 
Galakturia, 464 
Gallstones in the feces, 204 

analysis of, 205 
Gangrene of the lung, 269 
Garrod's test for uric acid in the blood, 

50 
Gases in the blood, 28 
in the feces, 190 
in the gastric contents, 164 
in the urine, 461 
Gastric contents, examination of, 112. 
• See also Gastric Juice ) 
juice, 112 

acetic acid in, 161 

acidity of, 120 

amount of, 119 

antiseptic properties of, 126 

aspiration of 117 

butyric acid in, 161 

cause of acidity of, 120 

chemical composition of, 120 

examination of, 120 
chymosin in, 145 
chymosinogen in, 145 
expression of, 116 
fatty acids in, 161 
ferments in, 141, 145 
free acids in, 129 
gases in, 164 

general characteristics of, 118 
hyperacidity of, 129 
hypersecretion of, 119, 125 
indirect examination of, 177, 

178 
lactic acid in, 153 
method of determining the total 

acidity of, 122 
methods of obtaining, 116 
milk-curdling ferment of, 145 
organic acids in, 161 
pepsin in, 141 
pepsinogen in, 141 
proteids in, 147 
ptomains and toxalbumins in , 

167 
secretion of, 112 
zymogens in, 141, 145 
digestion, products of, 147 

of albuminoids, 149 
of carbohydrates, 149 
of native albumins, 147 
analysis of products of, 151 
ulcer, 179 
Gastritis, acute, 179 
atrophic, 179 



INDEX. 



555 



Gastritis, chronic, L79 

mucous, 179 
Gastrosucorrhoea mucosa, 169 
Gigantoblasts Bee Riegaloblasts), 50 
Glanders, bacillus of 85 
Glucose, L09 

Bottger'e tost for, 417 

differential density method of 
estimating, in the urine, 424 

Kinhorn's method, 425 

Folding's method, 42L 
test for, 416 

in the blood, 28, 45 
estimation of, 46 
fermentation test, 417 

Xylander's test, 417 

phenyl-hydrazin test, 418 

polarimetric method, 419, 425 

quantitative estimation of, 421 

tests for, 415 

Trommer's test for, 415 
Glycogen in the blood, 47 

in the sputum, 268 

test for, 47 
Glycosuria, 409 

alimentaire, 410 

digestive, 410 

persistent, 412 

transitory, 411 
Glycosuric acid, 445 
Gmelin's reaction, 441 
Gonococcus in the blood, 84 

in the mouth, 106 

in urethral discharge, 507 

of Neisser, 507 

staining of, 508 
Gonorrhoea in the female, 536, 539 

in the male. 488, 507 
Gonorrhceal stomatitis, 106 

threads in the urine, 488 
Gowers' ha?moglobinometer, 35 
Gram's method of staining, 109 
y-granulations of Ehrlich, 65 
Grape sugar (see Glucose), 409 
Grethe's method of staining tubercle ba- 
cilli in the urine, 507 
Guaiacum test for blood, 409 
Guanin in the urine, 370 
Gum, animal, 429 
Gunning's mixture, 346 
Gunzburg's packages, 177 

reagent, 131 
Gymecophorus, 99 



HiEMATEMESIS, 171 
Haernatin, 38, 438 
Haematinuria, 391 
Haematoblasts, 71 
Hsematoidin in the blood, 41 
in the sputum, 266 
in the urine, 478 
Haeinatokrit, 76 



Bsematoporphyrin in the blood, 41 

in tin- urine, 138 
Hsematoporphyrinuria, 42 
Kflematuria, 393, 138, 489 
Elsemin (see Teichmann'a crystals), 3 ( .> 
Hsemocytometer of Thoma-Zeiss, 71 
1 hemoglobin, 17, 29 
carbon dioxide, 38 
monoxide, 37 
estimation of, with Fleischl's osmo- 
meter, 32 
with Gowers' lnemoglobinome- 
ter, 35 
nitric oxide, 38 
sulphuretted hydrogen, 38 
tests for, 408 

in the urine, 391 
Hnemoglobinaemia, 36, 391 
Haemoglobinometer of Gowers', 35 
Hemoglobinuria, 36, 391 
Flaemometer of Fleischl, 32 
Halitus sanguinis, 18 
Hammerschlag's method, 19 
Haycraft's method of estimating uric 

acid, 356 
Hayem's fluid, 72 
Heart disease, cells of, 272 

sputum in, 272 
Hehner-Seemann's method of estimating 

organic acids, 163 
Heintze's method of estimating uric acid, 

360 
Heller's test for albumin, 396 

for blood, 409 
Hepatogenic icterus, 440 
Heteroxanthin in the urine, 370 
Hippuric acid in the urine, 362, 471 
estimation of, 364 
properties of, 363 
test for, 364 
Histon in the urine, 394 

test for, 394 
Hoffmann's test for tyrosin, 476 
Hofmeister's method of estimating hip- 
puric acid, 365 
test for leucin, 476 
Homialomyia, 210 
Homogentisinic acid, 446 
Hopkins' method of estimating uric acid. 

355 
Hiifner's apparatus for the estimation of 

urea, 343 
Huppert's test for bile-pigment, 441 
Hydatid cysts, 523 

echinococcus membranes and 

hooklets in, 523 
sodium chloride in, 523 
succinic acid in, 523 
Hydrobilirubin, L97 
Hydrocele fluid, 513 

cholesterin in, 514 
Hydrochinon in the urine, 445 
Hydrochloric acid in the gastricjuice, 125 



556 



INDEX. 



Hydrochloric acid, according to Leo, 140 
to Martius and Liittke, 137 
to Topfer, 135 

amount of, 128 

combined, 134 

free, 126 

quantitative estimation of, 135 

significance of, 126 

source of, 125 

tests for, 130 
Hydrocyanic acid poisoning, blood 

changes in, 38 
Hydronephrosis, 523 
Hydro-paracumaric acid, 446 
Hydrothionuria, 461 
Hypalbuminosis, 44 
Hyperalbuminosis, 44 
Hyperchlorhydria, 129 
Hyperinosis, 44 
Hyperisotonia, 27 
Hyperleucocytosis, 58 
pathologic, 60 
physiologic, 58 
Hypersecretio acida et continua, 125, 129 
Hypersecretion, 129 
Hypinosis, 44 
Hypobromite solution, 336 
Hypochlorhydria, 129 
Hypoleucocytosis, 58 
Hypoxanthin in the urine, 371 



TCTEKUS, 440 

1 hematogenic, 440 

hepatogenic, 440 

neonatorum, 440 

urobilin, 443 
Idiopathic bacteriuria, 509 

oxaluria, 374 
Ilasvay's reagent, 103 
Indican in the urine, 432 
test for, 180, 435 
Indicanuria, 179, 432 
Indigo- blue in the urine, 434, 461, 480 

-red in the urine, 436 
Indigosuria, 434, 461 
Indol in the feces, 193 
tests for, 193 
Indoxyl, 316 

sulphate (see Indican ), 432 
Influenza, bacillus of, 86, 264 
Infusoria in the feces, 209, 216 

in the pus, 518 

in the vaginal discharge, 536 
Inosit in the urine, 429 
Insects in the feces, 210, 228 
Intermittent albuminuria, 378 
Intestinal catarrh, 238 

concretions, 205 

putrefaction, 178, 191, 432 

tuberculosis, 232 
Intestines, diseases of, 238 
Iodine in the urine, test for, 436 



Iodoform-test for lactic acid, 158 
Iodospermin, 534 
Iron test, 201 
Isotonia, 27 



TAFFE'S test for indican, 180, 435 
J Jaundice (see Icterus), 440 



KELLING'S test for lactic acid, 157 
Kjeldahl's method, 345 
Knapp's method, 423 
Korczynski and Jaworski's test, 201 
Krabbea grandis, 222 
Kreatin, 366 

properties of, 366 
Kreatinin, 366 

estimation of, 368 
properties of, 367 
test for. 368 
-zinc chloride, 367 
Kriiger-Wulff method of estimating 
alloxur bases, 371 



LACTIC acid, bacillus of, 153 
fermentation, 156 
in the blood, 51 
in the gastric contents, 153 

clinical significance of, 

153 
estimation of, 159 
mode of formation, 153 
tests for, 156 
Boas', 158 
Kelling's, 157 
Strauss', 157 
Uffelmann's, 156 
in the urine, 458 
Lactodensimeter of Quevenne , 545 
Lactoscope of Feser, 546 
Lactose in the urine, 427 
Laiose in the urine, 428 
Landois' estimation of the alkalinity of 

the blood, 22 
Latent microbism, 79 
Laveran's organism, 88 
Laverania malarise, 94 
Lecithin in the blood, 28 
Legal's test for acetone, 455 
Leo's method of estimating hydrochloric 

acid, 140 
Leprosy, bacillus of, 261 
Leptothrix buccalis, 108 

pulmonalis, 269 
Leube's test, 176 
Leucin, 267, 475 
Leucocytes, 57 

basophilic, 65 

differentiation according to their be- 
havior toward aniline dyes, 63 
Ehrlich's granulations in, 63 






INDEX. 



557 



Leucocytes, enumeration of, 74 
eosinophilic) 64 

estimation of tin 1 number of, 7 1, 75 
genera] differentiation of the various 

tonus of, (i'J 

indirect enumeration of, 75 

in the blood. 59 
in the exudates, : >17 
in the feces, 208 
in the sputum, 254 

in the urine, 485 

large mononuclear, 63 

lymphocytes, 63 

Mastzellen, 65 

myelocytes, ,;: > 

myelogenic, 65 

neutrophilic, 64 

polymorphonuclear, 64 

polynuclear, 64 

small mononuclear, 63 

transition forms, 63 

variations in number of, 58 
Leucocytosis, 58 

digestive form of, 59 
Leukemia, blood in, 100 
Levulose in the urine, 428 
Lieben's test for acetone, 455 
Lientery, 202 
Lipacida?mia, 50 
Lipaciduria, 459 
Lipa?rnia, 50 
Lipuria. 459. 47^ 
Liver abscess, 270 

acute yellow atrophy of, 329 

diseases of, feces in (see Acholic 
stools), urine in (see Bile-pig- 
ment- |. 
Lochia, 537 

alba, 538 

rubra, 537 
Loftier' s bacillus, 110 

methylene-blue solution, 109 
L'wvs method of estimating the alka- 
linity of the blood, 24 
Ludwig-Salkowski's method for estimat- 
ing uric acid, 358 
Lymphocytes, 63 



MACROCYTILKMIA, 54 
Magnesia mixture, 312 

soaps of, in the urine, 477 
Magnesium phosphate, 471, 479 
Malaria, plasmodium of, 88 
MalK.se, 102, 149 
Mammary secretion, 154 
Marrow cells, 65 

Marsh gas in the gastric contents, 165 
Martins' and Liittke's method for esti- 
mating hydrochloric acid, 137 
Mason's lung (see Siderosis>, 272 
Mastzellen, 65 
Meconium, 242 



Medico-legal test for blood, 40 
Megaloblasts, 56 
Megalocytes, 53 
Megastoma entericum, 216 
Melansemia, 97, 444 
Melanin in the urine, I 1 I 

tests for, 444 
Melanogen, 444 

Membranous dysmenorrhea, vaginal dis- 
charge in, 538 
Meningeal fluid, examination of, 525 
Menstruation, vaginal discharge in, 537 
Metalbumin in ovarian cysts, 521 

tests for, 521 
Metha?moglobin, 40 

sulphide, 38 
Methremoglobinsernia, 37, 40 
Methane (see Marsh Gas), 165 
Methylene-blue, 109 
Methyl-violet test, 132 
Micrococci in pus, 518 
Micrococcus gonorrhoeicus, 507 

urea?, 505 
Microcythaemia, 54 
Micro-organisms in the feces, 232 
in the milk, 544 
in the mouth, 103 
in the nasal secretion, 244 
in the pus, 518 
in the urine, 504 
in the vaginal discharge, 535 
Microscopic examination of the blood, 53 
of the buccal secretion, 103 
of cystic fluids, 521 
of exudates, 515, 517 
of the feces, 205 
of the gastric contents, 172 
of the nasal secretion, 244 
of the sputum, 254 
of transudates, 514 
of the urine, 465 
of the vaginal secretion, 535 
of the vomit, 172 
Miliary tuberculosis, urine in, 417 
Milk, 541 

chemical composition of, 543 

cow's, 543 

in disease, 544 

examination of, 545 

fat in, estimation of, 546 

human, 542 

secretion of, in the adult female, 
542 
in the newly born, 541 
specific gravity of, 545 
witches', 541 

-curdling ferment in the gastric 
juice, 145 
Millon's reagent, 406 
Mohr's test for hydrochloric acid, 133 
Motor-power of the stomach, examina- 
tion of, 175 
Leube's method, 176 



558 



INDEX. 



Motor-power, salol test of Ewald and 

Sievers, 176 
Mouth, actinomycosis of, 108 

secretions of, 101 

tuberculosis of, 108 
Mucin, in the feces, 234 

in the urine, 393 

test for, 407 
Mucous corpuscles in the urine, 275 

cylinders in the feces, 203, 240 
in the urine, 498 
Mucus, in the gastric contents, 167 

in the feces, 203, 207 
Muller- Weber's test for blood, 170 
Murexid test, 355, 467 
Myeline granules in the sputum, 256 
Myelocytes, 65 



XTASAL catarrh, 244 
Dl secretion, 244 

cerebro spinal fluid in, 244 
characteristics of, 244 
Charcot Leyden crystals in, 244 
concretions in, 244 
in disease. 244 
Neisser, gonococcus of, 507 
Nematodes, 209 
Nessler's reagent, 158 
Neusser's granules, 65 

stain, 70 
Neutral phosphate of calcium in the 

urine, 471 
Neutrophilic granules in the blood, 64 
Nitric acid test for albumin, 396 
Nitrites in the saliva, 103 
Nitrogen in the urine, 325 
estimation of, 345 

according to Kjeldahl, 345 
to Will-Varrentrapp, 
347 
Nitrogenous equilibrium, 327 
Nitro-prusside of sodium, as a test for 

acetone (see Legal' s test), 455 
Nitroso-indol reaction, 230 
Normal urobilin, 197, 430 
Normoblasts, 56 
Nose, secretion from, 244 
Nubecula in the urine, 275 
Nucleated red corpuscles, 56 
Nucleo-albumin, in the blood, 45 
in the urine, 393 
test for, 407 
Nylander's test for sugar, 417 



<E 



^DEMA of the lungs, sputum in, 271 
' Oidium albicans, 265 



Olefiant gas, 165 

Oligochromemia, 32 

Oligocythemia, 32 

Oliguria, 281 _ 

Organic acids in the blood, 48, 50 



Organic acids in the gastric juice, 161 

in the sputum, 267 

quantitative estimation of, 163 
Organized sediments of the urine, 481 
Ott's test, 408 
Ovarian cysts, 521 

Oxalate of calcium crystals in the spu- 
tum, 267 
in the urine, 468 
Oxalic acid in the urine, 373 

diathesis, 374 

properties of, 374 

quantitative estimation of, 375 

tests for, 375 
Oxaluria idiopathica, 374 
Oxy-acids in the urine, 445 
Oxyamygdalic acid, 446 
Oxybutyric acid-p in the urine, 458 
Oxyhemoglobin, 18, 29 
Oxyuris vermicularis, 225 
Ozena, 244 



PACINI'S fluid, 72 
Pancreatic cysts, 523 

trypsin in, 523 
juice in the gastric contents, 170 
Paracresol in the urine, 452 
Paramoecium coli, 216 
Para-oxy-phenyl-acetic acid, 446 

-glycolic acid, 446 
Parasites in the blood, 79 

in the feces, 187 

in the gastric contents, 171 

in the urine, 504 

malarial, 88 
Parasitology of the blood, 79 
Paraxanthin in the urine, 370 
Pathologic albuminuria, 379 

acetonuria, 453 

glycosuria, 412 

urobilin, 430, 442 
Pentoses in the urine, 428 
Pepsin in the gastric juice, 141 

estimation of, 144 

tests for, 143 
Pepsinogen in the gastric juice, 141 

estimation of, 144 

tests for. 144 
Peptones in the blood, 45 

in the feces, 234 

in the gastric contents, 148 

in the urine, 390 

tests for, 390, 406 
Peptonuria, 390 

enterogenic, 390 

hematogenic, 390 

hepatogenic, 390 

histogenic, 390 

pyogenic, 390 

renal, 390 

vesical, 390 
Pernicious anemia, 100 






INDEX. 



559 



Persistenl glycosuria, 412 
Pettenkofer'e test, 197 
Phagocytes, ~> s 
Phagocytosis, 58, 97 
Pharyngomycosis leptothrica, 108 
Phenol, L92, 445, 462 

estimation of, 452 

in the feces, 192 

in the urine, 4 15, 452 

tests for, 192, 445, 452 
Phenylglucosazon, 41V) 
Phenylhydrazin hydrochloride, 418 
Phloroglucin vanillin test for hydro- 
chloric acid, 131 
Phosphates in the urine, 305 

estimation of, 312 

separate estimation of alkaline and 
earthy, 315 

tests for, 311 
Phosphatic sediments in the urine, 462 
Phthisis pulmonalis, sputum in, 271 
Physiologic acetonuria, 453 

albuminuria, 376 

glycosuria, 409 
Picric-acid test for albumin, 401 
Pigments in the feces, 197 

in the urine, 429, 447 
Piria's test for tyrosin, 476 
Placenta sanguinis, 25 
Plaques. 7 1 

Plasma of the blood, 17, 26 
Plasmodium malarise, 88 

crescentic bodies, 94 

flagellate bodies, 96 

hyaline bodies, 90 

ovoid bodies, 94 

pigmented extra-cellular bodies, 

95 
intra-cellular bodies, 90 
segmenting bodies, 92 
spherical bodies, 94 
Plastic bronchitis, 269 
Platodes, 209 
Pneumaturia, 461 
Pneumoconioses, 272 
Pneumonia, diplococcus of, 81 

sputum in, 270 
Poikilocytes, 54 
Poikilocytosis, 54 
Polarimeter, 425 
Polycythemia, 
Polvrnastigina, 213 
Polyuria, 279 

epicritic form of, 280 
Preparation of cover-glasses, 66, 260 
Propep-in. 142 
Prostatic fluid, 531 
Proteids formed in the stomach, 147 

of the blood, 44 

reactions of, 152 
Proteoses, 148 
Proteus vulgaris, 84, 233 
Protozoa, 210 



Protozoa in the blood) 88 
in the feces, 21 <» 
in the pus, 519 

in the sputum. 259 

in the urine, 509 
Pseudo-casts, 198 

-gonococci, 508 

-leukemia, blood changes in, 100 
Psorospermosis, 217 
Ptomaine in the gastric contents, 167 

in the urine, 461 
Ptyalin, 102 

test for, 102 
Pulmonary diseases, sputum in, 268 

abscess, 269 

gangrene, 269 

• edema, 271 
Purulent exudates, 516 
Pus, 516 

chemistry of, 516 

crystals in, 519 

detritus in, 518 

general characteristics of, 516 

giant-corpuscles in, 518 

in the feces, 201 

in the gastric contents, 171 

in the urine, 485 

leucocytes in, 517 

microscopic examination of, 517 

parasites in, 518 

red corpuscles in, 518 

tests for, 486 
Putrescin, 161, 472 
Putrid bronchitis, 269 

exudates. 516 
Pycnometer, 286 
Pyogenic peptonuria, 390 
Pyrocatechin in the urine, 453 
Pyuria, 486 



Q 



UEVENXE'S lactodensimeter, 545 



REACTION of the blood, 21 
of the feces, 189, 199 

of the gastric juice, 120 

of the urine, 288 
Red blood-corpuscles, 17, 53 
Relapsing fever, spirillum of, 87 
Renal albuminuria, 380, 388 
Resorcin test, 132 

Resorptivc power of the stomach, ex- 
amination of, 176 
Reynolds' test for acetone, 455 
Rhinoliths, 211 
Rhizopoda, 210 
Rhubarb in the urine, 430 
Rice-water stools, 203 
Rosenbach's reaction, 436 

test for bile-pigments, 1 11 
Round worms, 217 



560 



INDEX. 



Boy's method of determining the specific 

gravity of the blood, 19 
Rust-colored expectoration, 248 



QACCHARIMETER of Einhorn, 419 
kJ of Soleil-Ventzke, 425 
Saccharomyces cerevisise (see Yeast). 
Sago-grain formations in the feces, 203 
Salicylic acid, test for, in the urine, 445 
Saliva, 101 

chemistry of, 101 

general characteristics of, 101 

in the gastric contents 169 

in special diseases of the mouth, 106 

microscopic examination of, 103 

nitiites in, 103 

pathologic alterations of, 105 

ptyalin in, 102 

test for nitrites, 103 
for ptyalin, 102 
for sulphocyanides, 102 
Salivary corpuscles in, 103 
Salivation, 105 
Salol, test for, in the urine, 445 

of Ewald and Sievers, 176 
Santonin in the urine, 430 
Sarcina pulmonalis, 265 

urinse, 506 

ventriculi, 173 
Scherer's test for leucin, 476 
Schistosoma, 99 
Schizomycetes in the feces, 187 
Schmaltz and Peiper's method of deter- 
mining the specific gravity of the 
the blood, 20 
Scybala, 198 
Sediments in the urine, 462 

ammonio-magnesium phosphate in, 
469, 479 

ammonium urate in, 479 

amorphous urates in, 467 

basic magnesium phosphate in, 471, 

m 

bilirubin in, 77 

calcium carbonate in, 480 

oxalate in, 468 

sulphate in, 472 
cystin in, 472 
epithelial cells in, 480 
fat in, 478 

foreign bodies in, 510 
hrematoidin in, 478 
hippuric acid in, 471 
in acid urines, 465 
in alkaline urines, 479 
indigo in, 480 
leucin in, 474 
leucocytes in, 485 
mode of examination of, 464 
monocalcium phosphate in, 470 
neutral calcium phosphate in, 471 
non organized, 465 



Sediments, organized, 481 

parasites in, 504 

red corpuscles in, 489 

soaps of lime and magnesia in, 477 

spermatozoa, 503 

tube-casts in, 492 

tumor-particles in, 510 

tyrosin in. 474 

urates in, 467 

uric acid in, 465 

xanthin in, 476 
Semen, 531 

chemistry of, 531 

general characteristics of, 531 

microscopic examination of, 532 

pathology of, 532 

recognition of, in stains, 533 

spermatic crystals in, 531 

spermatozoa in, 532 
Senna in the urine, 430 
Sepsis, organisms in the blood, 83 
Sero-purulent exudates, 514 
Serous exudates, 514 
Serum-albumin, in the blood, 25 
estimation of, 402 
in the urine, 376 
tests for, 396, 402 

-globulin, in the blood, 25 
estimation of, 406 
in the urine, 389 
test for, 405 
Siderosis, 272 
Skatol in the feces, 193 
Skatoxyl, 452 

sulphate, 452 
Smegma bacillus, 507 
Soaps of lime and magnesia in the urine, 

477 
Sodium chloride in hydatid fluid, 523 
I Spectroscope, 42 
Spermatic crystals, 531 
; Spermatocystitis, 504 
Spermatorrhoea, 504 
Spermatozoa in the semen, 532 

in the urine, 503 
Sperm in, 471, 475, 476 
Spiegler's reagent, 402 
Spirals of Curschmann, 252 
Spirillum of relapsing fever, 87 
Spirochseta Obermeieri, 87 
Sporozoa, 216 
Sputum, 245 

amount of, 246 

bacteria in, 260 

blood in, 248, 255 

cheesy particles in, 250 

chemistry of, 267 

color of, 247 

concretions in, 254 

configuration of, 249 

consistence of, 247 

Curschmann's spirals in, 252 

crudum, 249 



INDEX. 



.-,(51 



Sputum, crystals in. 265 

echinococcus membranes in, 254 
elastic tissue in, 250, 257 
fibrinous casts in, 250 

foreign bodies in, 254 
general characteristics of, 246 
globostnn, 249 
heterogeneous, 249 
homogeneous, 249 
in various diseases, 268 
macroscopic constituents, 250 
microscopic examination of, 254 
nummular, '1 19 
odor of, 248 
parasites, animal, in, 258 

vegetable, in, 260 
specific gravity of, 249 
technique in the examination of, 
245 
Staining of blood, 68 

of tubercle bacilli, 262 
Staphylococcus pyogenes albus, 84 
aureus, 84 
citreus, 84 
Starch, digestion of, 149 
Steatorrhea, 202 
Stercobilin, 197,442 
Stokes' fluid, 30 
Stomach, atrophy of, 179 
cancer of, 179 
dilatation of, 179 
motor-power of, 175 
rate of absorption in, 176 
-tube, 115 

contraindications to its use, 115 
its introduction, 115 
washing, 117 
Stomatitis, catarrhal, 106 
gonorrheal, 106 
ulcerative, 106 
Stools (see Feces). 
Strauss' test for lactic acid, 157 
Streptococcus pyogenes, 84 
brevis, 84 
conglomerate, 84 
longus, 84 
Strongyloides. 226 
Strongylus duodenalis, 226 
Stycosis, 272 

Succinic acid in hydatid fluid, 523 
Sugar in the blood, 28, 45 
in the urine. 409 
tests for, 4 1 5 
Sulphanilic acid test (see Ehrlich's reac- 
tion i 
Sulphates, estimation of, 321 
in the urine. 316, 452 
tests for, 320 
Sulphocyanides in the saliva, 102 
Sulphuretted hydrogen in the gastric 
contents, 165 
in the urine, 461 
tests for, 461 



Syntonin, 152 
tostfi tor, 152 



TAENIA cucumerina, 220 
diminuta, 220 
echinococcus, 258 
flavapunctata, 220 
mediocanellata, 217 
nana, 220 
saginata, 217 
solium, 218 
Tartar, 107 

Teichmann's crystals, 39 
Test-breakfast of Boas, 114 

of Ewald and Boas, 114 
-dinner of Riegel. 114 
-meal of Salzer, 114 
-meals, 113 
Thecosoma, 99 

Thoma-Zeiss' hsemoevtometer, 71 
Thrush, 106 
Titration method for estimating sugar, 

421, 423 
Toison's fluid, 72 
Tollens' reagent, 429 
Tongue, coating of, 107 
Tonsils, coating of, 108 
Toepfer's test for hydrochloric acid, 135 
Toxalbumins in the gastric contents, 167 
Transitory glycosuria, 411 
Transudates, 54 

albumin in, 512 
chemistry of, 513 
coagulation of, 513 
general characteristics of, 511 
microscopic examination of, 514 
specific gravity of, 511 
Trematodes, 222 
Tribromo-phenol, 453 
Trichina cystica, 97 

spiralis, 227 
Trichocephalus dispar, 227 
Trichomonas vaginalis, 21 4, 259, 509/536 
Trichotrachelides. 227 
Triple-phosphate crystals in the sputum, 
267 
in the urine, 469, 479 
Tripperfaden, 488 
Trommer's test, 415 

Tropfeolin test for hydrochloric acid, 132 
Trypsin in pancreatic cysts, 524 

test for, 524 
Tube-casts in the urine, 492 
amyloid, 497 

clinical significance of, 500 
compound hyaline, 493 
fatty, 497 
formation of, 499 
granular, 494 
hyaline. 493 

mode of examination of, 493 
pseudo-, 492 



36 



562 



INDEX. 



Tube-casts in the urine, pus, 486 
true, 493 
waxy, 497 
Tubercle bacilli, detection of, 260 
in the blood. 84 
in the feces, 232 
in the milk, 544 
in the pus, 519 
in the sputum, 260 
in the urine 507 
Tumor-particles in the gastric contents, 
175 
in the urine, 510 
Typhoid fever, bacillus of, 79, 231 
in the blood, 79 
in the feces, 242 
Ty rosin in the feces, 191 
in the sputum, 267 
in the urine, 474 
tests for, 476 



UFFELMANN'S test for lactic acid, 
156 
Ulcer of the stomach, 179 
Unorganized sediments in urines, 465 
Uraemia, 48 
Uranium solution, 313 
Urates in urinary sediments, 467, 479 
Urea in the blood. 48 
in the urine, 323 

estimation of, 336 
separation of, 334 
tests for, 335 
nitrate, 332 
oxalate, 333 
Ureometers, 336 
Doremus', 342 
Green's, 342 
Hufner's, 343 
Simon's, 336 
Squibb's, 344 
Urethritis, gonorrheal, 507 
Uric acid, 349 

crystals of, 465 
diathesis, 351 
estimation of, 49, 355 

Hay craft's method, 356 
Heintz's method, 360 
Hopkins' method, 355 
Ludwig-Salkowski's me- 
thod, 358 
in the blood, 48 
in the saliva, 105 
in the urine, 349, 465 
properties of, 353 
tests for, 355 
Urinary cylinders, 492 

sediments, 462 
Urine, 274 

acetone in, 453 
acidity of, 292 
albumins in, 376 



Urine, alkapton in, 445 

alloxur bases in, 371 

animal parasites in, 509 

benzoic acid in, 364 

bile acids in, 442 

pigments in, 439 

blood in, 438, 489 

carbohydrates in, 409 

casts in, 492 

chemistry of, 294 

chlorides in, 296 

chromogens in, 429 

chyle in, 393, 460, 479 

color of, 276 

consistence of, 278 

diacetic acid in. 457 

Ehrlich's reaction in, 447 

epithelium in, 480 

fat in, 459, 478 

fatty acids in, 459 

fecal matter in, 516 

ferments in, 460 

foreign bodies in, 510 

gases in, 461 

general appearance of, 275 

chemical composition of, 294 

hippuric acid in, 362 

indican in, 432 

kreatin in, 366 

kreatinin in, 366 

lactic acid in, 458 

leucocytes in, 485 

microscopic examination of, 465 

mineral ash, estimation of, 287 

nitrogen in, 325, 327 

nubecula in. 275 

odor of, 278 

organized sediments in, 481 

oxalic acid in, 373 

oxaluric acid in, 373 

oxy butyric acid in, 458 

parasites in, 504 

phenol in, 445, 452 

phosphates in, 305 

pigments in, 429 

ptomains, 461 

pus in, 486 

pyrocatechin in, 453 

quantity of, 278 

reaction of, 288 

sediments in, 462 

solids in, 287 

specific gravity of, 282 

spermatozoa in, 503 

sugar in. 409 

sulphates in, 316, 452 

urea in, 323 

vegetable parasites in, 504 

xanthin bases in, 370 
Urines, blue, 446 

green, 446 
Urinometer, 285 
Urobilin, febrile, 197, 443 



INDEX. 



563 



Urobilin, normal, 1 ( .»7. 430 
pathologic, 430, 4 12 
tests for, 143, 

( ierhardt"- 443 

v. Jaksch'a 443 
CJrobilinogen, 442 

Urobilinuria, I 13 
Urochrome, 430 
Troery thrin. 431 
(Jrofuscohsematm, 438 
Urohsematin, 436 
Drohsematoporphyririj 438 
CJroleucinic acid. 445 
Qrorosein, 437 
Uroroseinogen, 437 
Urorubroha?matin, 438 
Urrhodinic acid, 445 



VAGINAL blennorrhea. 537 
» discharge, 535 

bacteria in, 535 

during menstruation, 537 

general description of, 535 

in abortion, 539 

in gonorrhoea, 536, 539 

in membranous dvsmenorrhoea, 

538 
in uterine cancer, 539 
in vaginitis, 538 
in vulvitis, 538 
parasites in, 535 
reaction of, 535 
Vaginitis exfoliativa, 538 
Valeur globulaire, 35 
Vermes, in the blood, 97 
in the feces. 217 
in the sputum, 258 
in the urine, 510 
Vital i's test for pus, 486 



Vomited material, 167 
bile in, 170 
blood in, 170 
food material in, 167 

mucus in, L69 

odor of, 172 

pancreatic juice in, 170 

parasites in, 171 

pus in, 17 I 

saliva in, 169 

stercoraceous material in, 171 
Vomitus matutinus, 169 
v. Fleischl's ha?mometer 32 

WAXY casts, 497 
Weigert-Ehrlich stain, 262 

Weyl'8 test for kreatinin, 368 

Whetstone crystals (see Uric acid), 465 

White blood corpuscles (see Leucocytes), 
57 

Whooping-cough, sputum in, 264 

Worms (see Vermes), 217 

Widal's serum-test, 79 

Will-Varrentrapp's method of determin- 
ing nitrogen, 347 

XANTHIN bases in the blood, 50 
in the urine, 372, 476 
Xantho-proteic reaction, 193 

YEAST-CELLS in the gastric contents, 
173 
in the urine, 509 



ZIEHL-NEELSEX'S stain, 263 
Zymogens in the gastric juice, 141, 
145 



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